Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.bbrc.2021.04.022

Language：English   Publishing type：Research paper (scientific journal)  

Taste information is detected by taste cells and then transmitted to the brain through the taste nerve fibers. According to our previous data, there may be specific coding of taste quality between taste cells and nerve fibers. However, the molecular mechanisms underlying this coding specificity remain unclear. The purpose of this study was to identify candidate molecules that may regulate the specific coding. GeneChip analysis of mRNA isolated from the mice taste papillae and taste ganglia revealed that 14 members of the cadherin superfamily, which are important regulators of synapse formation and plasticity, were expressed in both tissues. Among them, protocadherin-20 (Pcdh20) was highly expressed in a subset of taste bud cells, and co-expressed with taste receptor type 1 member 3 (T1R3, a marker of sweet- or umami-sensitive taste cells) but not gustducin or carbonic anhydrase-4 (markers of bitter/sweet- and sour-sensitive taste cells, respectively) in circumvallate papillae. Furthermore, Pcdh20 expression in taste cells occurred later than T1R3 expression during the morphogenesis of taste papillae. Thus, Pcdh20 may be involved in taste quality-specific connections between differentiated taste cells and their partner neurons, thereby acting as a molecular tag for the coding of sweet and/or umami taste.

DOI： 10.1038/s41598-020-58991-8

Language：English   Publishing type：Research paper (scientific journal)  

Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders. We investigated the effects of a combination of three anticancer drugs (TPF: docetaxel, cisplatin and 5-fluorouracil) on the structure and function of mouse taste tissues and examined whether the drinking of ice-cold water after TPF administration would attenuate these effects. TPF administration significantly increased the number of cells expressing apoptotic and proliferative markers. Furthermore, TPF administration significantly reduced the number of cells expressing taste cell markers and the magnitudes of the responses of taste nerves to tastants. The above results suggest that anticancer drug-induced taste dysfunction may be due to a reduction in the number of taste cells expressing taste-related molecules. The suppressive effects of TPF on taste cell marker expression and taste perception were reduced by the drinking of ice-cold water. We speculate that oral cryotherapy with an ice cube might be useful for prophylaxis against anticancer drug-induced taste disorders in humans.

DOI： 10.3390/ijms21238958

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/nu11092251

Language：English   Publishing type：Research paper (scientific journal)  

Class C G protein– coupled receptors (GPCRs) are obligatory dimers that are particularly important for neuronal responses to endogenous and environmental stimuli. Ligand recognition through large extracellular domains leads to the reorganization of transmembrane regions to activate G protein signaling. Although structures of individual domains are known, the complete architecture of a class C GPCR and the mechanism of interdomain coupling during receptor activation are unclear. By screening a mutagenesis library of the human class C sweet taste receptor subunit T1R2, we enhanced surface expression and identified a dibasic intracellular retention motif that modulates surface expression and co-trafficking with its heterodimeric partner T1R3. Using a highly expressed T1R2 variant, dimerization sites along the entire subunit within all the structural domains were identified by a comprehensive mutational scan for co-trafficking with T1R3 in human cells. The data further reveal that the C terminus of the extracellular cysteine-rich domain needs to be properly folded for T1R3 dimerization and co-trafficking, but not for surface expression of T1R2 alone. These results guided the modeling of the T1R2–T1R3 dimer in living cells, which predicts a twisted arrangement of domains around the central axis, and a continuous folded structure between transmembrane domain loops and the cysteine-rich domains. These insights have implications for how conformational changes between domains are coupled within class C GPCRs.

DOI： 10.1074/jbc.RA118.006173

Language：English   Publishing type：Research paper (scientific journal)  

Expression of insulin and its receptor (IR) in rodent taste cells has been proposed, but exactly which types of taste cells express IR and the function of insulin signaling in taste organ have yet to be determined. In this study, we analyzed expression of IR mRNA and protein in mouse taste bud cells in vivo and explored its function ex vivo in organoids, using RT-PCR, immunohistochemistry, and quantitative PCR. In mouse taste tissue, IR was expressed broadly in taste buds, including in type II and III taste cells. With using 3-D taste bud organoids, we found insulin in the culture medium significantly decreased the number of taste cell and mRNA expression levels of many taste cell genes, including nucleoside triphosphate diphosphohydrolase-2 (NTPDase2), Tas1R3 (T1R3), gustducin, carbonic anhydrase 4 (CA4), glucose transporter-8 (GLUT8), and sodium-glucose cotransporter-1 (SGLT1) in a concentration-dependent manner. Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) signaling, diminished insulin’s effects and increase taste cell generation. Altogether, circulating insulin might be an important regulator of taste cell growth and/or proliferation via activation of the mTOR pathway.

DOI： 10.1371/journal.pone.0225190

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アンジオテンシンIIは、視床下部、副腎や血管などに発現するAT1受容体を介して、血圧や体内Na+濃度を調節する鍵ホルモンとして知られている。我々は、このアンジオテンシンIIが末梢の味覚器にも働き、塩味感受性を低下させ NaCl溶液の摂取量を増加させること、さらに甘味感受性を増強することで糖分摂取にも影響することを明らかにした。この“味覚を介したNa+/糖ホメオスタシス維持機構”のさらなる解明は、高血圧や肥満・糖尿病などの生活習慣病に対する新たな予防・治療法の開発”に繋がることが期待される。

Language：English   Publishing type：Research paper (scientific journal)  

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DOI： 10.1093/chemse/bji046

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DOI： 10.1093/chemse/bjh125

Language：English   Publishing type：Research paper (scientific journal)  

Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures.

Shigemura N, Ohta R, Kusakabe Y, Miura H, Hino A, Koyano K, Nakashima K, Ninomiya Y.

Section of Oral Neuroscience, and Section of Removable Prosthesis, Faculty of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-Pref. 812-8582, Japan, National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan, Bio-oriented Technology Research Advancement Institution (BRAIN), 3-18-19 Toranomon Minato-ku, Tokyo 105, Japan and Department of Chemistry, Asahi University School of Dentistry, 1851 Hozumi, Motosu, Gifu 501-0296, Japan.

Leptin is a hormone that regulates body weight homeostasis mainly via the hypothalamic functional leptin receptor, Ob-Rb. Recently, we proposed that the taste organ is a new peripheral target for leptin. Leptin selectively inhibits mouse taste cell responses to sweet substances, and thereby may act as a sweet taste modulator. The present study further investigated leptin action on the taste system by examining expression of Ob-Rb in taste cells and behavioral responses to sweet substances in leptin-deficient ob/ob, and Ob-Rb-deficient db/db mice and their normal litter mates. RT-PCR analysis showed that Ob-Rb was expressed in taste cells in all strain tested. The db/db mice, however, had a RT-PCR product containing an abnormal db-insertion which leads to an impaired shorter intracellular domain. In situ hybridization analysis showed that the hybridization signals for normal Ob-Rb mRNA were detected in taste cells in lean and ob/ob mice but not in db/db mice. Two different behavioral tests, one using sweet-bitter mixtures as taste stimuli, and the other a conditioned taste aversion paradigm, demonstrated that responses to sucrose and saccharin were significantly decreased after intraperitoneal injection of leptin in ob/ob and normal litter mates, but not in db/db mice. These results suggest that leptin suppresses behavioral responses to sweet substances through its action on Ob-Rb in taste cells. Such taste modulation by leptin may be involved in regulation for food intake.

DOI： 10.1210/en.2003-0602

Language：English   Publishing type：Research paper (scientific journal)  

Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds.

Shigemura N, Miura H, Kusakabe Y, Hino A, Ninomiya Y.

Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.

Leptin is a hormone that regulates food intake, energy expenditure and body weight. Our previous studies have demonstrated that the taste organ is a new peripheral target for leptin in mice. Leptin selectively inhibits the responses of taste nerves and receptor cells to sweet substances without affecting responses to sour, salty, and bitter substances. Still, there is no convincing evidence for the existence of leptin receptors (Ob-Rs) in taste receptor cells, especially the functional isoform Ob-Rb. We investigated the expression of 5 different Ob-R isoforms (a-e) and 6 STAT (signal transducers and activators of transcription) members in mouse taste cells. STATs are considered to be involved in the leptin signaling via Ob-Rb. Semiquantitative RT-PCR analysis showed that Ob-Rb was expressed in the taste buds of the fungiform and circumvallate papillae, but not so clearly in the surrounding epithelial tissue. The expression pattern among the three different tissues was similar to that of the taste cell specific G-protein, alpha-gustducin. The other Ob-R isoforms were widely detected in either the taste papillae or the epithelial tissue. Among 6 STAT members, STAT3 showed the highest relative abundance of mRNA in the taste buds. Consistently, in situ hybridization analysis showed that while Ob-Rb and STAT3 signals were detected in some taste bud cells, the signals were not clearly observed in the epithelial tissue cells. In conclusion, the present study provides evidence of the existence of the leptin receptor, Ob-Rb, and STAT3 in the mouse taste bud cells. This finding further confirms the involvement of leptin in the control of taste sensitivities to sweet substances in mice.

DOI： 10.1679/aohc.66.253

Language：English   Publishing type：Research paper (scientific journal)  

Leptin and sweet taste.
Ninomiya Y, Shigemura N, Yasumatsu K, Ohta R, Sugimoto K, Nakashima K, Lindemann B.
Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Leptin, the product of the obese (ob) gene, is a hormone primarily produced in adipose cells, and also at smaller amounts in some other peripheral organs. It regulates food intake, energy expenditure, and body weight. Leptin is thought to promote weight loss, at least in rodents, by suppressing appetite and stimulating metabolism. Mutant mice that lack either leptin or functional leptin receptors, such as ob/ob and db/db mice, are hyperphagic, massively obese, and diabetic. Central hypothalamic targets are mainly responsible for the effects of leptin on food intake and weight loss. However, there are also direct effects on peripheral tissues. Recently, the taste organ was found to be one of the peripheral targets for leptin. The hormone specifically inhibits sweet taste responses in lean mice and not in db/db mice. Thus leptin appears to act as a modulator of sweet taste, provided a functional leptin receptor is expressed by the taste cells. This chapter reviews the genetics and molecular biology of leptin and its receptors, the receptor mechanisms for sweet taste, the modulating action of leptin on taste receptor cells, and the consequences for the regulation of food intake.
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DOI： 10.1016/S0083-6729(02)64007-5

Publisher：Current Oral Health Reports  

Purpose of Review: Sweet-taste receptors play a crucial role in maintaining biological homeostasis by acting as energy sensors. However, the dynamics of this receptor after binding remain unknown because previous studies have primarily examined the static binding of the sweet taste receptor in complex with ligands. This review focuses on the mechanisms underlying the allostery-mediated activation and inactivation of the transmembrane domain of the sweet taste receptor subunit, TAS1R3. Recent Findings: Molecular dynamics simulations predicted that agonist binding induces the opening of the ionic lock formed by transmembrane helices III and VI. These simulations were validated by functional assays in HEK293 cells expressing the sweet taste receptor. Summary: The allostery through the interaction between the transmembrane domain of TAS1R3 and agonist would induce the conformational change on the intracellular side of the receptor, facilitating binding with the Gα subunit.

DOI： 10.1007/s40496-024-00391-2

Scopus

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.anl.2023.12.009

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DOI： 10.1002/1873-3468.14695.

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DOI： 10.3390/nu15132941.

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DOI： 10.1007/s00441-023-03756-8.

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Language：English   Publishing type：Research paper (scientific journal)  

© 2020 Elsevier B.V. Bitter taste receptors TAS2Rs detect noxious compounds in the oral cavity. Recent heterologous expression studies reported that some compounds function as antagonists for human TAS2Rs. For examples, amino acid derivatives such as γ-aminobutyric acid (GABA) and Nα,Nα-bis(carboxymethyl)-L-Lysine (BCML) blocked responses to quinine mediated by human TAS2R4. Probenecid inhibited responses to phenylthiocarbamide mediated by human TAS2R38. In this study, we investigated the effects of these human bitter receptor antagonists on behavioral lick responses of mice to elucidate whether these compounds also function as bitter taste blockers. In short-term (10 s) lick tests, concentration-dependent lick responses to bitter compounds (quinine-HCl, denatonium and phenylthiourea) were not affected by the addition of GABA or BCML. Probenecid reduced aversive lick responses to denatonium and phenylthiourea but not to quinine-HCl. In addition, taste cell responses to phenylthiourea were inhibited by probenecid. These results suggest some bitter antagonists of human TAS2Rs can work for bitter sense of mouse.

DOI： 10.1016/j.neulet.2020.135041

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s40496-020-00266-2

Language：English   Publishing type：Research paper (scientific journal)  

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Sweet taste thresholds are positively related to plasma leptin levels in normal weight humans: both show parallel diurnal variations and associations with postprandial glucose and insulin rises. Here, we tested whether this relationship also exists in overweight and obese (OW/Ob) individuals with hyperleptinemia. We tested 36 Japanese OW/Ob subjects (body mass index (BMI) > 25 kg/m2 ) for recognition thresholds for various taste stimuli at seven different time points from 8:00 a.m. to 10:00 p.m. using the staircase methodology, and measured plasma leptin, insulin, and blood glucose levels before each taste threshold measurement. We also used the homeostatic model assessment of insulin resistance (HOMA-IR) to evaluate insulin resistance. The results demonstrated that, unlike normal weight subjects, OW/Ob subjects showed no significant diurnal variations in the recognition thresholds for sweet stimuli but exhibited negative associations between the diurnal variations of both leptin and sweet recognition thresholds and the HOMA-IR scores. These findings suggest that in OW/Ob subjects, the basal leptin levels (~20 ng/mL) may already exceed leptin’s effective concentration for the modulation of sweet sensitivity and that this leptin resistance-based attenuation of the diurnal variations of the sweet taste recognition thresholds may also be indirectly linked to insulin resistance in OW/Ob subjects.

DOI： 10.3390/nu10030297

Language：English   Publishing type：Research paper (scientific journal)  

© 2017 IBRO Bitter taste serves as an important signal for potentially poisonous compounds in foods to avoid their ingestion. Thousands of compounds are estimated to taste bitter and presumed to activate taste receptor cells expressing bitter taste receptors (Tas2rs) and coupled transduction components including gustducin, phospholipase Cβ2 (PLCβ2) and transient receptor potential channel M5 (TRPM5). Indeed, some gustducin-positive taste cells have been shown to respond to bitter compounds. However, there has been no systematic characterization of their response properties to multiple bitter compounds and the role of transduction molecules in these cells. In this study, we investigated bitter taste responses of gustducin-positive taste cells in situ in mouse fungiform (anterior tongue) and circumvallate (posterior tongue) papillae using transgenic mice expressing green fluorescent protein in gustducin-positive cells. The overall response profile of gustducin-positive taste cells to multiple bitter compounds (quinine, denatonium, cyclohexamide, caffeine, sucrose octaacetate, tetraethylammonium, phenylthiourea, L-phenylalanine, MgSO4, and high concentration of saccharin) was not significantly different between fungiform and circumvallate papillae. These bitter-sensitive taste cells were classified into several groups according to their responsiveness to multiple bitter compounds. Bitter responses of gustducin-positive taste cells were significantly suppressed by inhibitors of TRPM5 or PLCβ2. In contrast, several bitter inhibitors did not show any effect on bitter responses of taste cells. These results indicate that bitter-sensitive taste cells display heterogeneous responses and that TRPM5 and PLCβ2 are indispensable for eliciting bitter taste responses of gustducin-positive taste cells.

DOI： 10.1016/j.neuroscience.2017.10.047

Language：English   Publishing type：Research paper (scientific journal)  

© 2017 Yoshida, Shin, Yasumatsu, Takai, Inoue, Shigemura, Takiguchi, Nakamura and Ninomiya. Cholecystokinin (CCK) is a gut hormone released from enteroendocrine cells. CCK functions as an anorexigenic factor by acting on CCK receptors expressed on the vagal afferent nerve and hypothalamus with a synergistic interaction between leptin. In the gut, tastants such as amino acids and bitter compounds stimulate CCK release from enteroendocrine cells via activation of taste transduction pathways. CCK is also expressed in taste buds, suggesting potential roles of CCK in taste signaling in the peripheral taste organ. In the present study, we focused on the function of CCK in the initial responses to taste stimulation. CCK was coexpressed with type II taste cell markers such as Ga-gustducin, phospholipase Cß2, and transient receptor potential channel M5. Furthermore, a small subset (~30%) of CCK-expressing taste cells expressed a sweet/umami taste receptor component, taste receptor type 1 member 3, in taste buds. Because type II taste cells are sweet, umami or bitter taste cells, the majority of CCK-expressing taste cells may be bitter taste cells. CCK-A and -B receptors were expressed in both taste cells and gustatory neurons. CCK receptor knockout mice showed reduced neural responses to bitter compounds compared with wild-type mice. Consistently, intravenous injection of CCK-Ar antagonist lorglumide selectively suppressed gustatory nerve responses to bitter compounds. Intravenous injection of CCK-8 transiently increased gustatory nerve activities in a dose-dependent manner whereas administration of CCK-8 did not affect activities of bitter-sensitive taste cells. Collectively, CCK may be a functionally important neurotransmitter or neuromodulator to activate bitter nerve fibers in peripheral taste tissues.

DOI： 10.3389/fphys.2017.00866

Language：English   Publishing type：Research paper (scientific journal)  

Background Gymnemic acids, triterpene glycosides, are known to act as human-specific sweet inhibitors. The long-lasting effect of gymnemic acids is diminished by γ-cyclodextrin. Here, we focus on the molecular mechanisms underlying the interaction between gymnemic acids and sweet taste receptor and/or γ-cyclodextrin by a sweet taste receptor assay in transiently transfected HEK293 cells. Highlight Application of gymnemic acids inhibited intracellular calcium responses to sweet compounds in HEK293 cells expressing human TAS1R2+TAS1R3 but not in those expressing the mouse sweet receptor Tas1r2+Tas1r3 after application of gymnemic acids. The effect of gymnemic acids was reduced after rinsing cells with γ-cyclodextrin. Based on species-specific sensitivities to gymnemic acids, we showed that the transmembrane domain of hTAS1R3 is involved in the sensitivity to gymnemic acids. Point mutation analysis in the transmembrane domain of hTAS1R3 revealed that gymnemic acids shared the same binding pocket with another sweet inhibitor, lactisole. Sensitivity to sweet compounds was also reduced by mixtures of glucuronic acid, a common gymnemic acid. In our molecular models, gymnemic acids interacted with a binding site formed in the transmembrane domain of hTAS1R3. Conclusion Gymnemic acids inhibit sweet responses in humans through an interaction between the glucuronosyl group of gymnemic acids and the transmembrane domain of hTAS1R3. Our molecular model provides a foundation for the development of taste modifiers.

DOI： 10.1016/j.job.2017.05.004

Language：English   Publishing type：Research paper (scientific journal)  

© 2016 IBRO Leptin is an important hormone that regulates food intake and energy homeostasis by acting on central and peripheral targets. In the gustatory system, leptin is known to selectively suppress sweet responses by inhibiting the activation of sweet sensitive taste cells. Sweet taste receptor (T1R2 + T1R3) is also expressed in gut enteroendocrine cells and contributes to nutrient sensing, hormone release and glucose absorption. Because of the similarities in expression patterns between enteroendocrine and taste receptor cells, we hypothesized that they may also share similar mechanisms used to modify/regulate the sweet responsiveness of these cells by leptin. Here, we used mouse enteroendocrine cell line STC-1 and examined potential effect of leptin on Ca2+ responses of STC-1 cells to various taste compounds. Ca2+ responses to sweet compounds in STC-1 cells were suppressed by a rodent T1R3 inhibitor gurmarin, suggesting the involvement of T1R3-dependent receptors in detection of sweet compounds. Responses to sweet substances were suppressed by ⩾1 ng/ml leptin without affecting responses to bitter, umami and salty compounds. This effect was inhibited by a leptin antagonist (mutant L39A/D40A/F41A) and by ATP gated K+ (KATP) channel closer glibenclamide, suggesting that leptin affects sweet taste responses of enteroendocrine cells via activation of leptin receptor and KATP channel expressed in these cells. Moreover, leptin selectively inhibited sweet-induced but not bitter-induced glucagon-like peptide-1 (GLP-1) secretion from STC-1 cells. These results suggest that leptin modulates sweet taste responses of enteroendocrine cells to regulate nutrient sensing, hormone release and glucose absorption in the gut.

DOI： 10.1016/j.neuroscience.2016.06.036

Language：English   Publishing type：Research paper (scientific journal)  

The primary sweet sensor in mammalian taste cells for sugars and noncaloric sweeteners is the heteromeric combination of type 1 taste receptors 2 and 3 (T1R2+T1R3, encoded by Tas1r2 and Tas1r3 genes). However, in the absence of T1R2+T1R3 (e.g., in Tas1r3 KO mice), animals still respond to sugars, arguing for the presence of T1Rindependent detection mechanism(s). Our previous findings that several glucose transporters (GLUTs), sodium glucose cotransporter 1 (SGLT1), and the ATP-gated K+ (KATP ) metabolic sensor are preferentially expressed in the same taste cells with T1R3 provides a potential explanation for the T1R-independent detection of sugars: sweet-responsive taste cells that respond to sugars and sweeteners may contain a T1R-dependent (T1R2+T1R3) sweet-sensing pathway for detecting sugars and noncaloric sweeteners, as well as a T1Rindependent (GLUTs, SGLT1, KATP ) pathway for detecting monosaccharides. However, the T1R-independent pathway would not explain responses to disaccharide and oligomeric sugars, such as sucrose, maltose, and maltotriose, which are not substrates for GLUTs or SGLT1. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we found that taste cells express multiple α-glycosidases (e.g., amylase and neutral α glucosidase C) and so-called intestinal "brush border" disaccharide-hydrolyzing enzymes (e.g., maltase-glucoamylase and sucrase-isomaltase). Treating the tongue with inhibitors of disaccharidases specifically decreased gustatory nerve responses to disaccharides, but not to monosaccharides or noncaloric sweeteners, indicating that lingual disaccharidases are functional. These taste cell-expressed enzymes may locally break down dietary disaccharides and starch hydrolysis products into monosaccharides that could serve as substrates for the T1R-independent sugar sensing pathways.

DOI： 10.1073/pnas.1520843113

Language：English   Publishing type：Research paper (scientific journal)  

Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice. The sweet taste induced by MCL is more intense when acidification occurs with weak acids as opposed to strong acids. MCL interacts with the human sweet receptor subunit hTAS1R2, but the mechanisms by which the acidification of MCL activates the sweet taste receptor remain largely unexplored. The work reported here speaks directly to this activation by utilizing a sweet receptor TAS1R2 + TAS1R3 assay. In accordance with previous data, MCL-applied cells displayed a pH dependence with citric acid (weak acid) being right shifted to that with hydrochloric acid (strong acid). When histidine residues in both the intracellular and extracellular region of hTAS1R2 were exchanged for alanine, taste-modifying effect of MCL was reduced or abolished. Stronger intracellular acidification of HEK293 cells was induced by citric acid than by HCl and taste-modifying effect of MCL was proportional to intracellular pH regardless of types of acids. These results suggest that intracellular acidity is required for full activation of the sweet taste receptor by MCL.

DOI： 10.1038/srep22807

Language：Others  

© 2015 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved. Background Several studies have demonstrated that some gut peptides known to be important in energy metabolism are expressed in mouse taste bud cells. However, the functions of these peptides in taste cells are still largely unknown. In the gut, one of these peptides, glucagon-like peptide-1 (GLP-1), which is known as the insulinotropic gut peptide, is secreted from enteroendocrine L-cells, which express as many taste molecules as those on the tongue. These taste transduction molecules are suggested to be involved in GLP-1 secretion from L-cells in response to various nutrient stimuli. GLP-1 is reported to function as a neurotransmitter via activation of its receptors expressed on the vagus nerve, thereby regulating insulin secretion. Highlight Consistent with this evidence from the gastrointestinal tract, recent studies have demonstrated that GLP-1 is secreted from mouse taste cells in response to taste compounds such as sugars, artificial sweeteners, and long-chain fatty acids. GLP-1 secreted from taste cells may activate particular types of gustatory nerve fibers because they express GLP-1 receptors and respond to GLP-1 administered via the femoral vein. Conclusion GLP-1 released from taste cells may be involved in transmission of sweet and lipid signals, thereby impacting animalsfeeding behavior in response to these important nutrient factors.

DOI： 10.1016/j.job.2015.09.002

Language：Others  

© 2016 Elsevier Inc. All rights reserved. Taste receptor cells sense various chemical compounds in foods and transmit these signals through gustatory nerve fibers to the central nervous system. These sensory signals are vitally important for life; they provide information about which prospective foods are nutritious and warnings as to those that are noxious. Recent studies have revealed the involvement of multifarious bioactive peptides, many of which are primarily identified organs such as the gastrointestinal tract, in the modulation of taste responses. These peptides affect peripheral taste responsiveness of animals and play important roles in the regulation of feeding behavior and the maintenance of homeostasis. In this chapter, we discuss the various functions of peptide signaling in the peripheral taste system.

DOI： 10.1016/B978-0-12-801694-7.00017-2

Language：English   Publishing type：Research paper (scientific journal)  

© 2015 by the American Diabetes Association. Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, themolecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds.

DOI： 10.2337/db14-1462

Language：English   Publishing type：Research paper (scientific journal)  

© 2015 The Physiological Society. Leptin is an anorexigenic mediator that reduces food intake by acting on hypothalamic receptor Ob-Rb. In contrast, endocannabinoids are orexigenic mediators that act via cannabinoid CB1 receptors in hypothalamus, limbic forebrain, and brainstem. In the peripheral taste system, leptin administration selectively inhibits behavioural, taste nerve and taste cell responses to sweet compounds. Opposing the action of leptin, endocannabinoids enhance sweet taste responses. However, potential roles of endogenous leptin and endocannabinoids in sweet taste remain unclear. Here, we used pharmacological antagonists (Ob-Rb: L39A/D40A/F41A (LA), CB1: AM251) and examined the effects of their blocking activation of endogenous leptin and endocannabinoid signalling on taste responses in lean control, leptin receptor deficient db/db, and diet-induced obese (DIO) mice. Lean mice exhibited significant increases in chorda tympani (CT) nerve responses to sweet compounds after LA administration, while they showed no significant changes in CT responses after AM251. In contrast, db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid (2-arachidonoyl-sn-glycerol (2-AG)) levels in the taste organ, and enhanced expression of a biosynthesizing enzyme (diacylglycerol lipase α (DAGLα)) of 2-AG in taste cells. In DIO mice, the LA effect was gradually decreased and the AM251 effect was increased during the course of obesity. Taken together, our results suggest that circulating leptin, but not local endocannabinoids, may be a dominant modulator for sweet taste in lean mice; however, endocannabinoids may become more effective modulators of sweet taste under conditions of deficient leptin signalling, possibly due to increased production of endocannabinoids in taste tissue.

DOI： 10.1113/JP270295

Language：English   Publishing type：Research paper (scientific journal)  

© FASEB. Five fundamental taste qualities (sweet, bitter, salty, sour, umami) are sensed by dedicated taste cells (TCs) that relay quality information to gustatory nerve fibers. In peripheral taste signaling pathways, ATP has been identified as a functional neurotransmitter, but it remains to be determined how specificity of different taste qualities is maintained across synapses. Recent studies demonstrated that some gut peptides are released from taste buds by prolonged application of particular taste stimuli, suggesting their potential involvement in taste information coding. In this study, we focused on the function of glucagon-like peptide-1 (GLP-1) in initial responses to taste stimulation. GLP-1 receptor (GLP-1R) null mice had reduced neural and behavioral responses specifically to sweet compounds compared to wild-type (WT) mice. Some sweet responsive TCs expressed GLP-1 and its receptors were expressed in gustatory neurons. GLP-1 was released immediately from taste bud cells in response to sweet compounds but not to other taste stimuli. Intravenous administration of GLP-1 elicited transient responses in a subset of sweet-sensitive gustatory nerve fibers but did not affect other types of fibers, and this response was suppressed by pre-administration of the GLP-1R antagonist Exendin-4(3-39). Thus GLP-1 may be involved in normal sweet taste signal transmission in mice.

DOI： 10.1096/fj.14-265355

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Gymnemic acids are triterpene glycosides that selectively suppress taste responses to various sweet substances in humans but not in mice. This sweet-suppressing effect of gymnemic acids is diminished by rinsing the tongue with γ-cyclodextrin (γ-CD). However, little is known about the molecular mechanisms underlying the sweet-suppressing effect of gymnemic acids and the interaction between gymnemic acids versus sweet taste receptor and/or γ-CD. To investigate whether gymnemic acids directly interact with human (h) sweet receptor hT1R2 + hT1R3, we used the sweet receptor T1R2 + T1R3 assay in transiently transfected HEK293 cells. Similar to previous studies in humans and mice, gymnemic acids (100 μg/ml) inhibited the [Ca2+]iresponses to sweet compounds in HEK293 cells heterologously expressing hT1R2 + hT1R3 but not in those expressing the mouse (m) sweet receptor mT1R2 + mT1R3. The effect of gymnemic acids rapidly disappeared after rinsing the HEK293 cells with γ-CD. Using mixed species pairings of human and mouse sweet receptor subunits and chimeras, we determined that the transmembrane domain of hT1R3 was mainly required for the sweet-suppressing effect of gymnemic acids. Directed mutagenesis in the transmembrane domain of hT1R3 revealed that the interaction site for gymnemic acids shared the amino acid residues that determined the sensitivity to another sweet antagonist, lactisole. Glucuronic acid, which is the common structure of gymnemic acids, also reduced sensitivity to sweet compounds. In our models, gymnemic acids were predicted to dock to a binding pocket within the transmembrane domain of hT1R3.

DOI： 10.1074/jbc.M114.560409

Language：English  

Taste receptor cells play a major role in detection of chemical compounds in the oral cavity. Information derived from taste receptor cells, such as sweet, bitter, salty, sour and umami is important for evaluating the quality of food components. Among five basic taste qualities, sweet taste is very attractive for animals and influences food intake. Recent studies have demonstrated that sweet taste sensitivity in taste receptor cells would be affected by leptin and endocannabinoids. Leptin is an anorexigenic mediator that reduces food intake by acting on leptin receptor Ob-Rb in the hypothalamus. Endocannabinoids such as anandamide [N-arachidonoylethanolamine (AEA)] and 2-arachidonoyl glycerol (2-AG) are known as orexigenic mediators that act via cannabinoid receptor 1 (CB1) in the hypothalamus and limbic forebrain to induce appetite and stimulate food intake. At the peripheral gustatory organs, leptin selectively suppresses and endocannabinoids selectively enhance sweet taste sensitivity via Ob-Rb and CB1 expressed in sweet sensitive taste cells. Thus leptin and endocannabinoids not only regulate food intake via central nervous systems but also modulate palatability of foods by altering peripheral sweet taste responses. Such reciprocal modulation of leptin and endocannabinoids on peripheral sweet sensitivity may play an important role in regulating energy homeostasis. © 2012 Elsevier Ltd.

DOI： 10.1016/j.semcdb.2012.08.004

Language：English   Publishing type：Research paper (scientific journal)  

The oral perception of fat has traditionally been considered to rely mainly on texture and olfaction, but recent findings suggest that taste may also play a role in the detection of long chain fatty acids. The two G-protein coupled receptors GPR40 (Ffar1) and GPR120 are activated by medium and long chain fatty acids. Here we show that GPR120 and GPR40 are expressed in the taste buds, mainly in type II and type I cells, respectively. Compared with wild-type mice, male and female GPR120 knock-out and GPR40 knock-out mice show a diminished preference for linoleic acid and oleic acid, and diminished taste nerve responses to several fatty acids. These results show that GPR40 and GPR120 mediate the taste of fatty acids. Copyright © 2010 the authors.

DOI： 10.1523/JNEUROSCI.0496-10.2010

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Background: The peptide gurmarin is a selective sweet response inhibitor for rodents. In mice, gurmarin sensitivity differs among strains with gurmarin-sensitive C57BL and gurmarin-poorly-sensitive BALB strains. In C57BL mice, sweet-responsive fibers of the chorda tympani (CT) nerve can be divided into two distinct populations, gurmarin-sensitive (GS) and gurmarin-insensitive (GI) types, suggesting the existence of two distinct reception pathways for sweet taste responses. By using the dpa congenic strain (dpa CG) whose genetic background is identical to BALB except that the gene(s) controlling gurmarin sensitivity are derived from C57BL, we previously found that genetically-elevated gurmarin sensitivity in dpa CG mice, confirmed by using behavioral response and whole CT nerve response analyses, was linked to a greater taste cell population co-expressing sweet taste receptors and a Gα protein, Gα-gustducin. However, the formation of neural pathways from the increased taste cell population to nerve fibers has not yet been examined.Results: Here, we investigated whether the increased taste cell population with Gα-gustducin-coupled sweet receptors would be associated with selective increment of GS fiber population or nonselective shift of gurmarin sensitivities of overall sweet-responsive fibers by examining the classification of GS and GI fiber types in dpa CG and BALB mice. The results indicated that dpa CG, like C57BL, possess two distinct populations of GS and GI types of sweet-responsive fibers with almost identical sizes (dpa CG: 13 GS and 16 GI fibers; C57BL: 16 GS and 14 GI fibers). In contrast, BALB has only 3 GS fibers but 18 GI fibers. These data indicate a marked increase of the GS population in dpa CG.Conclusion: These results suggest that the increased cell population expressing T1r2/T1r3/Gα-gustducin in dpa CG mice may be associated with an increase of their matched GS type fibers, and may form the distinct GS sweet reception pathway in mice. Gα-gustducin may be involved in the GS sweet reception pathway and may be a key molecule for links between sweet taste receptors and cell type-specific-innervation by their matched fiber class. © 2009 Yasumatsu et al; licensee BioMed Central Ltd.

DOI： 10.1186/1471-2202-10-152

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Multiple lines of evidence from molecular studies indicate that individual taste qualities are encoded by distinct taste receptor cells. In contrast, many physiological studies have found that a significant proportion of taste cells respond to multiple taste qualities. To reconcile this apparent discrepancy and to identify taste cells that underlie each taste quality, we investigated taste responses of individual mouse fungiform taste cells that express gustducin or GAD67, markers for specific types of taste cells. Type II taste cells respond to sweet, bitter or umami tastants, express taste receptors, gustducin and other transduction components. Type III cells possess putative sour taste receptors, and have well elaborated conventional synapses. Consistent with these findings we found that gustducin-expressing Type II taste cells responded best to sweet (25/49), bitter (20/49) or umami (4/49) stimuli, while all GAD67 (Type III) taste cells examined (44/44) responded to sour stimuli and a portion of them showed multiple taste sensitivities, suggesting discrimination of each taste quality among taste bud cells. These results were largely consistent with those previously reported with circumvallate papillae taste cells. Bitter-best taste cells responded to multiple bitter compounds such as quinine, denatonium and cyclohexamide. Three sour compounds, HCl, acetic acid and citric acid, elicited responses in sour-best taste cells. These results suggest that taste cells may be capable of recognizing multiple taste compounds that elicit similar taste sensation. We did not find any NaCl-best cells among the gustducin and GAD67 taste cells, raising the possibility that salt sensitive taste cells comprise a different population. © 2009 The Authors. Journal compilation © 2009 The Physiological Society.

DOI： 10.1113/jphysiol.2009.175075

Language：English   Publishing type：Research paper (international conference proceedings)  

Perception of sweet taste is important for animals to detect external energy source of calories. In mice, sweet-sensitive cells possess a leptin receptor. Increase of plasma leptin with increasing internal energy storage in the adipose tissue suppresses sweet taste responses via this receptor. Data from our recent studies indicate that leptin may also modulate sweet taste sensation in humans with a diurnal variation in sweet sensitivity. This leptin modulation of sweet taste information to the brain may influence individuals' preference and ingestive behavior, thereby playing important roles in regulation of energy homeostasis. © 2009 New York Academy of Sciences.

DOI： 10.1111/j.1749-6632.2009.03893.x

Language：English   Publishing type：Research paper (international conference proceedings)  

Recent molecular studies proposed that the T1r1T1r3 heterodimer, mGluR1 and mGluR4 might function as umami taste receptors in mice. However, the roles of each of these receptors in umami taste are not yet clear. In this paper, we summarize recent data for T1r3, mGluR1, and mGluR4 as umami taste receptors and discuss receptor systems responsible for umami detection in mice. © 2009 New York Academy of Sciences.

DOI： 10.1111/j.1749-6632.2009.03902.x

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

In rodents, section of the taste nerve results in degeneration of the taste buds. Following regeneration of the cut taste nerve, however, the taste buds reappear. This phenomenon can be used to study the functional reformation of the peripheral neural system responsible for sweet taste. In this study we examined the recovery of sweet responses by the chorda tympani (CT) nerve after nerve crush as well as inhibition of these responses by gurmarin (Gur), a sweet response inhibitor. After about 2 weeks of CT nerve regeneration, no significant response to any taste stimuli could be observed. At 3 weeks, responses to sweet stimuli reappeared but were not significantly inhibited by Gur. At 4 weeks, Gur inhibition of sweet responses reached statistically significant levels. Thus, the Gur-sensitive (GS) component of the sweet response reappeared about 1 week later than the Gur-insensitive (GI) component. Moreover, single CT fibers responsive to sucrose could be classified into distinct GS and GI groups at 4 weeks. After 5 weeks or more, responses to sweet compounds before and after treatment with Gur became indistinguishable from responses in the intact group. During regeneration, the GS and GI components of the sucrose response could be distinguished based on their concentration-dependent responses to sucrose. These results suggest that mice have two different sweet-reception systems, distinguishable by their sensitivity to Gur (the GS and GI systems). These two sweet-reception systems may be reconstituted independently during regeneration of the mouse CT nerve. © The Authors (2007).

DOI： 10.1111/j.1460-9568.2007.05761.x

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

It is known that a subset of taste cells generate action potentials in response to taste stimuli. However, responsiveness of these cells to particular tastants remains unknown. In the present study, by using a newly developed extracellular recording technique, we recorded action potentials from the basolateral membrane of single receptor cells in response to taste stimuli applied apically to taste buds isolated from mouse fungiform papillae. By this method, we examined taste-cell responses to stimuli representing the four basic taste qualities (NaCl, Na saccharin, HCl, and quinine-HCl). Of 72 cells responding to taste stimuli, 48 (67%) responded to one, 22 (30%) to two, and 2 (3%) to three of four taste stimuli. The entropy value presenting the breadth of responsiveness was 0.158 ± 0.234 (mean ± SD), which was close to that for the nerve fibers (0.183 ± 0.262). In addition, the proportion of taste cells predominantly sensitive to each of the four taste stimuli, and the grouping of taste cells based on hierarchical cluster analysis, were comparable with those of chorda tympani (CT) fibers. The occurrence of each class of taste cells with different taste responsiveness to the four taste stimuli was not significantly different from that of CT fibers except for classes with broad taste responsiveness. These results suggest that information derived from taste cells generating action potentials may provide the major component of taste information that is transmitted to gustatory nerve fibers. Copyright © 2006 The American Physiological Society.

DOI： 10.1152/jn.00409.2006

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Amiloride, a sodium channel blocker, is known to suppress NaCl responses of the chorda tympani (CT) nerve in various mammalian species. In mice, the NaCl suppressing effect of amiloride is reported to differ among strains. In C57BL mice, amiloride inhibits NaCl responses to about 50% of control, whereas no such clear suppression was evident in prior studies with 129 mice. However, evidence from behavioral studies is not entirely consistent with this. Recently, it has been found that genetic backgrounds of 129 mice differ within substrains. 129X1/SvJ (formerly 129/SvJ) mice differ from the 129P3/J (formerly 129/J) strain by 25% of sequence length polymorphisms. Therefore, we examined possible substrain difference between 129P3/J and 129X1/SvJ mice in the amiloride sensitivity of electrophysiologically recorded NaCl responses. Amiloride significantly suppressed CT responses to NaCl without affecting responses to KCl both in 129P3/J and 129X1/SvJ mice. However, the magnitude of the amiloride inhibition was significantly larger (∼50% of control in response to 0.01-1.0 M NaCl by 100 μM amiloride) in 129X1/SvJ than in 129P3/J mice (∼20% of control in response to 0.03-0.3 M NaCl by 100 μM amiloride). Threshold amiloride concentration for suppression of responses to 0.3 M NaCl was 30 μM in 129P3/J mice, which was higher than that in 129X1/SvJ mice (10 μM). In 129X1/SvJ mice, the threshold amiloride concentration eliciting inhibition of NaCl responses and the magnitude of the inhibition were comparable with those in C57BL/6 mice. These results suggest that amiloride sensitivity of NaCl responses differs even among the 129 substrains, 129P3/J and 129 X1/SvJ, and the substrain difference of 129 mice in amiloride sensitivity is as large as that between two inbred strains (129P3/J and C57BL/6). © 2006 Oxford University Press.

DOI： 10.1093/chemse/bjj061

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Gurmarin (Gur) is a peptide that selectively inhibits responses of the chorda tympani (CT) nerve to sweet compounds in rodents. In mice, the sweet-suppressing effect of Gur differs among strains. The inhibitory effect of Gur is clearly observed in C57BL/6 mice, but only slightly, if at all, in BALB/c mice. These two mouse strains possess different alleles of the sweet receptor gene, Sac(Tas1r3) (taster genotype for C57BL/6 and non-taster genotype for BALB/c mice), suggesting that polymorphisms in the gene may account for differential sensitivity to Gur. To investigate this possibility, we examined the effect of Gur in another Tas1r3 non-taster strain, 129X1/Sv mice. The results indicated that unlike non-taster BALB/c mice but similar to taster C57BL/6 mice, 129X1/Sv mice exhibited significant inhibition of CT responses to various sweet compounds by Gur. This suggests that the mouse strain difference in the Gur inhibition of sweet responses of the CT nerve may not be associated with polymorphisms of Tas1r3. © The Author 2005. Published by Oxford Universiry Press. All rights reserved.

DOI： 10.1093/chemse/bji041

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (international conference proceedings)  

DOI： 10.1093/chemse/bjh092

Language：English   Publishing type：Research paper (international conference proceedings)  

DOI： 10.1093/chemse/bjh114

Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

The db/db mouse has defective leptin receptors. The defects lead to impairments of leptin regulation of food intake and body weight, and result in the expression of diabetic symptoms such as hyperinsulinemia, hyperglicemia, and extreme obesity. Recent studies have proposed that leptin may also affect memory and learning processes. To examine this possibility, we compared the ability of leptin-receptor-deficient db/db mice and their normal lean litter mates to form and extinguish a conditioned taste aversion (CTA) for saccharin. We used a short-term (10s) lick test and a long-term (48h) two bottle preference test for measurement of consumption of test solutions. On the first day after conditioning to avoid saccharin, the db/db mice showed preference scores for saccharin as low, and aversion thresholds for sucrose lower than that of the lean mice. During the extinction test trials beginning from the second up to the 30th day after conditioning, numbers of licks and preference scores for aversive saccharin and sucrose appeared to be larger, and recovered faster to the control levels in db/db mice. These results indicate that db/db mice with leptin-receptor-deficiency may show equal capacity to form CTAs for saccharin, greater generalization from saccharin to sucrose, and a faster rate of extinction. This suggests that disruption of leptin signalling does not inhibit acquisition of CTA learning, but impairs its extinction. This differential contribution of the leptin system on CTA processes may be due to differential distribution of leptin receptors in the CTA-related brain areas. © 2003 Elsevier Science (USA). All rights reserved.

DOI： 10.1016/S1074-7427(03)00046-7

Language：English   Publishing type：Research paper (scientific journal)  

Gurmarin (Gur) is a peptide that selectively suppresses responses of the chorda tympani nerve to sweet substances in rats and mice. In the present study, we examined the effect of Gur on behavioral responses to sweet substances in C57BL mice. To accomplish this, we developed a new short-term lick test and measured numbers of licks for 10 s for sweet substances mixed with quinine hydrochloride (QHCI) in water-deprived mice. Numbers of licks for sucrose mixed with 1 or 3 mM QHCI increased with increasing concentration of sucrose from 0.01 to 1.0 M. Oral infusion with 30 μg/ml Gur produced significant decreases in responses to concentration series for sucrose mixed with 3 mM QHCI, whereas no such effect by Gur was observed in responses to QHCI alone or QHCI-mixed HCI, NaCI or monosodium glutamate. The Gur suppression of QHCI-mixed sucrose responses, which otherwise lasted for 2-3 h, rapidly returned to ∼80% of control levels after oral infusion with β-cyclodextrin. These results are comparable to neural data previously found in chorda tympani responses, and thereby provide further evidence for Gur as a sweet response inhibitor in C57BL mice. In the other aspect, our newly developed short-term test can also provide a tool for measurements of taste-guided behavioral responses to sweeteners. © Oxford University Press 2003. All rights reserved.

DOI： 10.1093/chemse/28.3.237

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Others   Publishing type：Research paper (other academic)  

Leptin, a hormone released from the adipose tissue, inhibits food intake and increases energy expenditure. We have found a novel function of leptin as a modulator of sweet taste sensitivity in mice. In lean normal mice, the gustatory nerve responses to sweet stimuli were selectively suppressed depending on plasma leptin level after an intraperitoneal injection of recombinant leptin. Patch-clamp studies using isolated taste cells of lean mice showed that extracellular leptin enhanced K+ currents of sweet-responsive taste cells, which led to membrane hyperpolarization and a reduction of sweetener-induced depolarization. Reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization analyses demonstrated specific expression of mRNA of the long-form functional leptin receptor (Ob-Rb) in taste tissue and cells of lean mice. The genetically diabetic db/db mice, which have defects in Ob-Rb, demonstrated neither a suppression of gustatory neural responses to sweeteners nor an increment of whole-cell K+ conductance of taste cells even with high doses of leptin. These results suggest that Ob-Rb is specifically expressed in sweet-responsive taste cells of lean mice and that leptin suppresses sweetener-induced depolarization via activation of K+ channels, leading to a decrease in impulses of sweet-best fibers. The enhanced sweet responses of db/db mice may result from the lack of inhibitory modulation by leptin.

DOI： 10.1351/pac200274071141

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Localization of activated caspase-3-positive and apoptotic cells in the developing tooth germ of the mouse lower first molar.
Shigemura N, Kiyoshima T, Sakai T, Matsuo K, Momoi T, Yamaza H, Kobayashi I, Wada H, Akamine A, Sakai H.
Laboratory of Oral Pathology and Medicine, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
This study examined the immunohistochemical detection of activated caspase-3, and its association with apoptosis, during tooth morphogenesis of the mouse lower first molar. The distribution of cells positive for caspase-3 closely corresponded with the localization of the terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate-biotin nick end labelling (TUNEL)-positive apoptotic cells through the developmental course of tooth germs from embryo day 12 (E12) to E19, thus showing that the apoptosis occurring in the developing odontogenic tissue was induced by the activation of the caspase family. The specific distribution pattern of apoptotic cells in the developing odontogenic epithelial tissue from the initiation (E12) of tooth germ to the completion of tooth crown morphology (E19) also suggests that apoptotic events are related not only to a deletion of functionally suspended cells, but also participate in initiation and the completion of tooth morphogenesis. Electron microscopic examination revealed that apoptotic cells were present in the primary enamel knot, and these apoptotic cells were phagocytized by neighbouring odontogenic epithelial cells, thus indicating the prompt disposal of any dead cells by epithelial cells.

DOI： 10.1023/A:1017900305661

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Detection of differentially expressed genes in the early developmental stage of the mouse mandible.
Yamaza H, Matsuo K, Kiyoshima T, Shigemura N, Kobayashi I, Wada H, Akamime A, Sakai H.
Department of Oral Pathology, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
We previously examined the development of the mouse mandible, and demonstrated that odontogenesis occurs between embryonic day 10.5 (E10.5) and E12. Based on the histological findings, we performed cDNA subtraction between the E10.5 and E12 mandibles to detect any differentially expressed genes which might be involved in the initiation of odontogenesis. By sequencing, homology search and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), we thus found Pgk-1, Ccte, Hsp86, Nucleolin, Hsc73, Frg1, N-ras, Set alpha and Hsj2 from the E10.5 mandible, and E25, ATPase6, Mum2, Thymosin beta4 and L21 from the E12 mandible to be differentially expressed genes. These genes are functionally related to protein transport, signal transduction, transcription, translation and molecular chaperon activity. In situ hybridization analyses of Set alpha and E25 showed that Set alpha was detected in the tooth germ at E12 and E14.5, thus indicating a close relationship of this gene to odontogenesis. Meanwhile, the in situ signal of E25 was found in the muscular layer of the tongue, thus suggesting E25 to be related to the differentiation of muscular tissue. In conclusion, we found 15 differentially expressed genes in the course of the early developmental stage of the mouse mandible using a combination of the cDNA subtraction and semi-quantitative RT-PCR methods, while in addition, two genes were demonstrated to be related to the initiation and the development of both tooth germ and the tongue according to the in situ hybridization technique.

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese  

Language：Others   Publishing type：Research paper (scientific journal)  

Immunohistochemical and ultrastructural findings in a rare case of papillary cyst-adenocarcinoma arising from the left sublingual gland of a 55-year-old Japanese man are reported. Histologically, the tumor tissue was found to be composed of various-sized cystic cavities in which papillary epithelial projections with thin fibrovascular cores were observed. The papillary projections consisted of a single layer to several layers of high columnar epithelial cells. Invasion to the surrounding fibrous tissue and into the lymphatics was observed, thus suggesting an aggressive potential in the present case. The possibility of the involvement of myoepithelial cells could be excluded based on the immunohistochemical and ultrastructural findings. The immunohistochemical and ultrastructural findings also suggested that this type of salivary gland tumor, at least the present case, may arise from striated or excretory ducts. There was positive immunostaining for tumor markers CA19-9 and CA125. However, the biological role of these carbohydrate antigens in salivary gland tumors is unclear at present. Further investigations are, therefore, called for to solve this issue.

DOI： 10.1111/j.1600-0714.1999.tb02040.x

Language：English   Publishing type：Research paper (scientific journal)  

The distribution of BrdU- and TUNEL-positive cells during odontogenesis in mouse lower first molars.
Shigemura N, Kiyoshima T, Kobayashi I, Matsuo K, Yamaza H, Akamine A, Sakai H.
Second Department of Conservative Dentistry, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
This study investigated the minute distribution of both proliferating and non-proliferating cells, and cell death in the developing mouse lower first molars using 5-bromo-2'-deoxyuridine (BrdU) incorporation and the terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate (dUTP)-biotin nick end labeling (TUNEL) double-staining technique. The distribution pattern of the TUNEL-positive cells was more notable than that of the BrdU-positive cells. TUNEL-positive cells were localized in the following six sites: (1) in the most superficial layer of the dental epithelium during the initiation stage, (2) in the dental lamina throughout the period during which tooth germs grow after bud formation, (3) in the dental epithelium in the most anterior part of the antero-posterior axis of the tooth germ after bud formation, (4) in the primary enamel knot from the late bud stage to the late cap stage, (5) in the secondary enamel knots from the late cap stage to the late bell stage, and (6) in the stellate reticulum around the tips of the prospective cusps after the early bell stage. These peculiar distributions of TUNEL-positive cells seemed to have some effect on either the determination of the exact position of the tooth germ in the mandible or on the complicated morphogenesis of the cusps. The distribution of BrdU-negative cells was closely associated with TUNEL-positive cells, which thus suggested cell arrest and the cell death to be essential for the tooth morphogenesis.

DOI： 10.1023/A:1003796023992

Responsible for pages：S70-71   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：7-28   Language：Japanese   Book type：General book, introductory book for general audience

Language：Japanese   Book type：General book, introductory book for general audience

本書は、味覚センサや匂いセンサが登場し、近年発展の著しいおいしさの科学を概観し、おいしさを数値化する科学技術を紹介、それらを応用した食ビジネスのグローバル展開に触れた世界で最初の成書である。その最初の第1章で、美味しさ基礎編「味覚受容機構」を概説した。

Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：13:58-63   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：21(2):120-125   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：34(4):371-378   Language：Japanese   Book type：General book, introductory book for general audience

Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：http://www.team-approach.net/myaccount/login.php?forward=/tokushu/article.php?id=50   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：364-6   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：vol.4-5: 14-18   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：26, 890-893   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：45 No3 158-160   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：第25章ホルモン　p251-276   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：9(2) : 177-183   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：107 No3 597-602   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：五つの基本味（塩味、酸味、苦味、甘味、うま味）：p63-70   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：T1R3-KOマウスの甘味・うま味受容体：新たな謎、21 (18): 2540-2541   Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：総ページ数：ix, 259p   Language：Japanese  

Language：Japanese   Book type：General book, introductory book for general audience

Responsible for pages：28(9):1405-8   Language：Japanese   Book type：General book, introductory book for general audience

Event date： 2022.8

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡市   Country：Japan  

Event date： 2022.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪市   Country：Japan  

Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡市   Country：Japan  

Event date： 2020.11

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：東京歯科大学（web）   Country：Japan  

本学会は、国際歯科研究学会（International Association for Dental Research：IADR）のSectionとして1954年11月6日に発足し、その後、会員の増加と活発な学会活動が認められIADRのDivisionに昇格し、Japanese Association for Dental Research（JADR）と称して今日に至っています。そして現在では、IADRのDivision/Sectionの中で世界第2位の規模を誇り、世界をリードする学術活動を展開しています。JADRは、その設立以来、歯科医学および関連分野の研究の促進を図り、口腔保健の向上に寄与するとともに、国際的視野にたってIADR の発展に貢献し、社会の公益に寄与することを目的としてきました。

Event date： 2020.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：筑波（web）   Country：Japan  

Event date： 2020.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：鹿児島   Country：Japan  

Event date： 2020.3 - 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Beppu(0ita)   Country：Japan  

Event date： 2018.4

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪   Country：Japan  

Event date： 2018.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

味覚は、食を通じて栄養物質を摂取する上で欠かせない感覚である。近年、5基本味（甘味、塩味、苦味、酸味、うま味）が、それぞれ特異的な味覚受容体により引き起こされ、さらに、その味覚感受性が液性因子により修飾されることが明らかになってきた。例えば、レプチン（摂食抑制因子）と内因性カンナビノイド（摂食亢進因子）は中枢に拮抗的に作用することで摂食を調節することが知られているが、両者が末梢の味覚器にも直接作用し、拮抗的に甘味感受性を修飾していることが明らかとなった。また、アンジオテンシンIIは、脳や腎臓に作用して体内ナトリウムの維持に重要な役割を担っているが、末梢の味覚器にもその受容体（AT1）を介して作用し、αENaC（アミロライド感受性塩味受容体）発現塩味細胞とT1r3（甘味受容体構成分子）発現甘味細胞の味覚感受性を修飾することも明らかとなった。これらの味覚修飾は味溶液に対する摂取行動にも影響することから、末梢における味覚発現およびその修飾は体内カロリーやナトリウムのホメオスタシス維持に重要な役割を担っていると考えられる。したがって、味覚システムの基本原理を理解することは摂食が関連する疾病（糖尿病・高血圧など）に対する新たな予防・治療法の開発に繋がるものと期待される。

Event date： 2018.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

食品の重要な要素であるおいしさと味について、人による官能評価が現在でも最も重要な方法である。個人差や環境などと客観性の維持、官能評価を行うパネルの確保、作業負担など大きな課題を抱えている。20世紀の最後に味覚受容体が発見され、21世紀の味覚の研究はドラスティックな変化を遂げている。
そこで今回はその最新知見として、味覚の受容・修飾機構（主に甘味と塩味）および生活習慣病（肥満や高血圧など）との連関について紹介する。

Event date： 2017.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：神戸   Country：Japan  

Naイオン（Na+）は、体液浸透圧の保持、神経の興奮など生命維持に不可欠な働きを担うため、体内Na+濃度は常に一定に保たれる必要がある。このNa+を外部から摂取するための主役が塩味受容機構である。しかし、この分子メカニズムの詳細については未だ不明な点が多い。塩味受容成分は少なくとも2つの成分：利尿剤アミロライドにより抑制される成分（amiloride sensitive: AS） と抑制されない成分 (amiloride insensitive: AI) に分類される。AS塩味受容体に関しては、近年、ENaCαサブユニットがその分子実体であることが明らかにされた。AS塩味感受性の多様性に関しては、αENaCの遺伝子多型性（single nucleotide polymorphisms: SNPs）が関与する可能性をマウスの遺伝学的解析から見出した。塩味の調節機構に関しては、血圧調節ホルモンであるアルドステロン（Aldo）に加えて、アンジオテンシンII（AngII）も味覚器に直接作用し、AS塩味感受性をAldoと連携して調節している可能性が示唆された。さらに、AngIIの産生に関わるレニン-アンジオテンシンシステム（RAS）が味蕾内に存在していることが明らかとなり、塩味感受性が味蕾内で迅速に調節されることで無駄のないNa+摂取が可能となっている可能性が示唆された。

Event date： 2017.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：fukuoka   Country：Japan  

Event date： 2017.1

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Fukuoka   Country：Japan  

味覚の全身における機能を紹介し、味覚異常が糖尿病や高血圧といった生活習慣病と深く関与している可能性について概説する。

Event date： 2016.8 - 2015.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：札幌   Country：Japan  

味覚は、外界から栄養物質を検知・摂取する上で欠かせない感覚である。近年、5基本味（甘味、塩味、苦味、酸味、うま味）が、それぞれ特異的な味覚受容体により引き起こされ、また、その味覚感受性が遺伝子変異により変化することや、液性因子により修飾されることも明らかになってきた。例えば、GPCRであるT1R1+T1R3へテロ二量体は、うま味受容体として機能しており、ヒトにおいてはその一塩基遺伝子多型性（SNPs）により味覚認知閾値が変化する。また、脳や腎臓に作用して体内ナトリウムの維持に重要な役割を担っているアンジオテンシンIIは末梢の味覚器にもその受容体（AT1）を介して作用し、αENaC（アミロライド感受性塩味受容体）発現塩味細胞とT1r3発現甘味細胞の味覚感受性を修飾することが明らかとなった。さらに近年、味覚システムが口腔のみならず小腸、膵臓や脳など様々な臓器で発現し、異なる機能を連携させることで効率的な栄養素代謝を可能にしていることが明らかになってきた。これらのことから、味覚システムの基本原理を理解することは摂食とその代謝機構が関連する生活習慣病（糖尿病、高血圧など）に対する新たな予防・治療法の開発に繋がるものと期待される。

Event date： 2016.3 - 2015.3

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：Yokohama   Country：Japan  

Event date： 2014.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Kagoshima   Country：Japan  

血圧を調節する鍵ホルモンであるアンジオテンシンIIは、中枢性に作用して塩分嗜好性を増強するのみならず、末梢の味覚器にも働き、塩味感受性を低下させ NaCl溶液の摂取量を増加させること、さらに甘味感受性を増強することで糖分摂取増加させることを明らかにした。また摂食調節因子であるレプチンと内因性カンナビノイドは中枢性に拮抗的に働くだけでなく、味覚器にも作用し、甘味感受性を拮抗的に調節することで、エネルギー摂取量を制御していることを明らかにした。以上のことから、新たなホルモンを介した脳-味覚連関による合目的な体内栄養維持機構が存在する可能性が示唆された。

Event date： 2013.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Fukuoka   Country：Japan  

Information derived from taste receptor cells, such as sweet, bitter, salty, sour and umami is important for evaluating the quality of food components. Modulation of the gustatory information influences food preference and intake. Even so, the molecular mechanisms for modulating taste sensitivity are poorly understood. Our recent studies have demonstrated that sweet and salty taste sensitivities are affected by hormones. Angiotensin II (AngII), which plays important roles in the maintenance of sodium homeostasis by acting on AngII type 1 receptor in various organs including brain and kidney, modulates peripheral salt and sweet taste sensitivities, and this modulation influences ingestive behavior in mice. Leptin (an anorexigenic mediator) and endocannabinoids (orexigenic mediators), which reciprocally regulate food intake via central nervous systems, modulate palatability of foods by altering sweet taste responses. Thus peripheral modulations of taste information by these hormones critically influence food intake, and may play important roles in regulating sodium and energy homeostasis. Understanding basic principles about these taste modulations may lead us to design novel strategies to maintain and improve the quality of life in patients with medical treatment.

Event date： 2012.9

Presentation type：Oral presentation (general)  

Venue：名古屋   Country：Japan  

Event date： 2011.11

Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：盛岡   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：Erlangen   Country：Germany  

Behavioral and molecular analyses in the dpa
(D-phenylalanine sensitivity) congenic strain

Shigemura Noriatsu1, Kawato Yuriko1, Furuta Hiroki2, Yoshida
Ryusuke2, and Ninomiya Yuzo2

1Sect. Oral Neurosci., Grad. Sch. Dental Sci., Kyushu Univ., Fukuoka,
Japan, 2Bio-oriented Tech. Res. Adv. Ins. (BRAIN), Saitama, Japan;
shigemura@dent.kyushu-u.ac.jp

Presentation type：Oral presentation (general)  

Venue：Kyushu University, Fukuoka   Country：Japan  

The dpa locus may influence behavioral and neural responses to umami

Noriatsu Shigemura1, Keiko Yasumatsu1,2 , Yuriko Kawato1,2 , and Yuzo Ninomiya 1,2
(1 Sect. of Oral Neurosci., Grad. Sch. of Dent. Sci., Kyushu Univ., 2 BRAIN)

Presentation type：Oral presentation (general)  

Venue：九大国際ホール   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：横浜、鶴見大学記念館   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：Sarasota   Country：United States  

Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：Tokyo   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：Fukuoka   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：Sarasota   Country：United States  

Event date： 2023.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2023.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2023.8

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2022.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：徳島市   Country：Japan  

Event date： 2022.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：徳島市   Country：Japan  

Event date： 2022.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：徳島市   Country：Japan  

Event date： 2022.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台市   Country：Japan  

Event date： 2022.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台市   Country：Japan  

Event date： 2022.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台市   Country：Japan  

Event date： 2022.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台市   Country：Japan  

Event date： 2022.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台市   Country：Japan  

Event date： 2022.3

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台市   Country：Japan  

Event date： 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡市   Country：Japan  

Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡市   Country：Japan  

Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡市   Country：Japan  

Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡市   Country：Japan  

Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡市   Country：Japan  

Event date： 2021.9 - 2021.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡市   Country：Japan  

Event date： 2021.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：名古屋（web）   Country：Japan  

Event date： 2020.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：筑波（web）   Country：Japan  

Event date： 2020.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：筑波（web）   Country：Japan  

Event date： 2020.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：筑波（web）   Country：Japan  

Event date： 2020.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：鹿児島   Country：Japan  

In this study, we thus focused on the HA signaling in taste bud maintenance. We first examined the expression of HA and its related molecules in mouse taste tissues by using immunostaining, in situ hybridization and quantitative RT-PCR. Moreover, we explored the function of HA signaling in taste bud organoids (in vitro) and in mouse taste tissues (in vivo) by using 4MU (4-methylumberifellone: a HA synthase inhibitor).

Event date： 2020.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：鹿児島   Country：Japan  

Event date： 2020.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：鹿児島   Country：Japan  

Event date： 2020.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：鹿児島   Country：Japan  

Event date： 2020.8

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Portland   Country：United States  

Event date： 2020.8

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Portland   Country：United States  

Event date： 2020.3 - 2019.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Beppu(0ita)   Country：Japan  

Event date： 2020.3 - 2019.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Beppu(0ita)   Country：Japan  

Event date： 2019.11

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Fukuoka   Country：Japan  

Event date： 2019.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2019.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2019.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：高知   Country：Japan  

Event date： 2019.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：高知   Country：Japan  

Event date： 2019.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：高知   Country：Japan  

Event date： 2019.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：高知   Country：Japan  

Event date： 2019.9

Language：English   Presentation type：Oral presentation (general)  

Venue：Trieste   Country：Italy  

Event date： 2019.6

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Vancouver   Country：Canada  

Event date： 2019.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Kobe   Country：Japan  

Event date： 2017.12

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Fukuoka   Country：Japan  

Event date： 2017.12

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Fukuoka   Country：Japan  

Event date： 2017.12

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Fukuoka   Country：Japan  

Event date： 2017.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：神戸   Country：Japan  

Event date： 2017.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：神戸   Country：Japan  

Event date： 2017.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：松本   Country：Japan  

Event date： 2017.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：松本   Country：Japan  

Event date： 2017.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：松本   Country：Japan  

Event date： 2017.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：hamamatsu   Country：Japan  

Event date： 2017.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：hamamatsu   Country：Japan  

Event date： 2017.2

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Fukuoka   Country：Japan  

Event date： 2016.12

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Fukuoka   Country：Japan  

Event date： 2016.8 - 2015.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：札幌   Country：Japan  

Event date： 2016.8 - 2015.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：札幌   Country：Japan  

Event date： 2016.6 - 2015.6

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Yokohama   Country：Japan  

Event date： 2016.6 - 2015.6

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Yokohama   Country：Japan  

Event date： 2016.6 - 2015.6

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Yokohama   Country：Japan  

Event date： 2016.6 - 2015.6

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Yokohama   Country：Japan  

Event date： 2016.3 - 2015.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Sapporo   Country：Japan  

Event date： 2015.11

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Fukuoka   Country：Japan  

Event date： 2015.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Kobe   Country：Japan  

Event date： 2015.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Kobe   Country：Japan  

Event date： 2015.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Kobe   Country：Japan  

Event date： 2015.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Kobe   Country：Japan  

Event date： 2015.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Kobe   Country：Japan  

Event date： 2015.2 - 2015.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：由布院   Country：Japan  

Event date： 2014.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：静岡   Country：Japan  

Event date： 2014.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：静岡   Country：Japan  

Event date： 2014.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：静岡   Country：Japan  

Event date： 2014.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：静岡   Country：Japan  

Event date： 2014.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：静岡   Country：Japan  

Event date： 2014.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Kagoshima   Country：Japan  

Event date： 2014.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Kagoshima   Country：Japan  

Event date： 2013.10

Language：English   Presentation type：Oral presentation (general)  

Venue：Fukuoka   Country：Japan  

Event date： 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台   Country：Japan  

Event date： 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：岡山   Country：Japan  

Event date： 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：岡山   Country：Japan  

Event date： 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：岡山   Country：Japan  

Event date： 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：岡山   Country：Japan  

Event date： 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台   Country：Japan  

Event date： 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台   Country：Japan  

Event date： 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台   Country：Japan  

Event date： 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台   Country：Japan  

Event date： 2013.7

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：New Orleans   Country：United States  

Event date： 2013.7

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：New Orleans   Country：United States  

Event date： 2013.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Tokyo   Country：Japan  

Event date： 2013.2

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Tokyo   Country：Japan  

Event date： 2012.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：岡崎   Country：Japan  

Event date： 2012.10

Presentation type：Symposium, workshop panel (public)  

Venue：大阪   Country：Japan  

Event date： 2012.10

Presentation type：Symposium, workshop panel (public)  

Venue：大阪   Country：Japan  

Event date： 2012.10

Presentation type：Symposium, workshop panel (public)  

Venue：大阪   Country：Japan  

Event date： 2012.10

Presentation type：Symposium, workshop panel (public)  

Venue：大阪   Country：Japan  

Event date： 2012.9

Presentation type：Symposium, workshop panel (public)  

Venue：郡山   Country：Japan  

Event date： 2012.8

Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：埼玉   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：広島市   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：北九州市   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：Vancouver   Country：Canada  

Presentation type：Oral presentation (general)  

Venue：松戸市   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：なら100年会館（奈良県）   Country：Japan  

Expression of receptors (Ob-Rb) and sweet-suppressive effects of leptin in the mouse taste buds.

Noriatsu Shigemura1, 2, Hirohito Miura2, 3, Yuko Kusakabe2, 3, Akihiro Hino2, 3, Kiyohito Nakashima4, Kumiko Sugimoto5 and Yuzo Ninomiya1, 2,

1Sect. Oral Neurosci., Grad. Sch. Dent. Sci., Kyushu Univ., Fukuoka 812-8582., 2 Bio-oriented Tech. Res. Adv. Ins. (BRAIN), Tokyo 105-0001, 3Nat. Food Res. Ins., Ibaraki 305-8642., 4Dep. Chem., Asahi Univ. Sch. Dent., Gifu 501-0223., 5Neurobiol., Grad. Sch. Dent., Tokyo Med. Dent. Univ., Tokyo 113-8549;

Presentation type：Symposium, workshop panel (public)  

Venue：国立京都国際会館（京都府）   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：高知県立県民分化ホール（高知県高知市）   Country：Japan  

Expression of leptin receptors isoforms (Ob-Rs) and STAT3 mRNA in mouse taste buds.

Noriatsu Shigemura1, 2, Hirohito Miura2, Akihiro Hino2, and Yuzo Ninomiya1, 2,

Section of Oral Neuroscience, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

Presentation type：Symposium, workshop panel (public)  

Venue：東京ビックサイト（東京都）   Country：Japan  

Leptin effects to sweet taste sensitivities in leptin-resistant db/db and ob/ob mice

Noriatsu Shigemura, Rie Ohta, Kiyohito Nakashima and Yuzo Ninomiya,

Sect. Oral Neurosci., and bSect. Remov. Prothedont., Grad. Sch. of Dent. Sci., Kyushu Univ., cDept. Chem., Asahi Univ. Sch. Dent., dBio-oriented Tech. Res. Adv. Ins. (BRAIN)

Presentation type：Symposium, workshop panel (public)  

Venue：鹿児島市民分化ホール（鹿児島県鹿児島市）   Country：Japan  

Behavioral and molecular analyses of dpa (D-phenylalanine sensitivity) locus in mice.

Noriatsu Shigemura1, Yuriko Kawato2 Kazushige Sasamoto and Yuzo Ninomiya1, 2,

1Sect. Oral Neurosci., Fac. Dent. Sci., Kyushu Univ., Fukuoka 812-8582.,
2 Bio-oriented Tech. Res. Adv. Ins. (BRAIN), Tokyo 105-0001

Presentation type：Symposium, workshop panel (public)  

Venue：学術総合センター／一橋記念講堂／学士会館／如水会館（東京都）   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：福岡国際会議場／福岡サンパレス／マリンメッセ福岡（福岡県福岡市）   Country：Japan  

Analysis of the dpa (D-phenylalanine sensitivity) locus in mice.

Noriatsu Shigemura1, Yuriko Kawato2 Kazushige Sasamoto and Yuzo Ninomiya1, 2,

1Sect. Oral Neurosci., Fac. Dent. Sci., Kyushu Univ., Fukuoka 812-8582.,
2 Bio-oriented Tech. Res. Adv. Ins. (BRAIN), Tokyo 105-0001

Presentation type：Symposium, workshop panel (public)  

Venue：名古屋国際会議場（名古屋市熱田区）   Country：Japan  

The site of action of the dpa (D-phenylalanine sensitivity) segment in mice

Noriatsu Shigemura1, Kiyohito Nakashima2, Keiko Yasumatsu1, Yuriko Kawato3 and Yuzo Ninomiya1,3

1Sect. Oral Neurosci., Grad. Sch. Dental Sci., Kyushu Univ. 2Dept. Chem., Asahi Univ. Sch. Dent. 3Bio-oriented Tech.Res.Adv.Ins. (BRAIN).

It is known that there are two loci influencing responses to sweet substances on mouse chromosome 4, dpa and Sac (Saccharin preference). Recent studies indicate that Sac encodes a G-protein-coupled sweet receptor, T1R3. However no such progress has been made for dpa. In this study, we investigated possible action of dpa segment by using the congenic strain (CG) having BALB background except the segment derived from C57 strain. Behavioral analysis demonstrated that sensitivities to 0.1 M sucrose in a conditioned taste aversion of D-Phenylalanine or to gurmarin (inhibitor for sweetener responses) and β-cyclodextrin (reducer for the effects of gurmarin) in responses to sweet substances were similarly observed in both CG and C57, not BALB. This suggests that the dpa segment in CG may contain a gene influencing gurmarin-sensitivity. We also examined the candidate dpa transduction elements in CG by using the cDNA subtraction and other possible methods.

Presentation type：Symposium, workshop panel (public)  

Venue：岡山県岡山市   Country：Japan  

dpa (D-phenylalanine sensitivity) locus may influence umami sensitivity.

Noriatsu Shigemura1, Yuriko Kawato2 Keiko Yasumatsu2 and Yuzo Ninomiya1, 2,

1Sect. Oral Neurosci., Fac. Dent. Sci., Kyushu Univ., Fukuoka 812-8582.,
2 Bio-oriented Tech. Res. Adv. Ins. (BRAIN), Tokyo 105-0001

Presentation type：Symposium, workshop panel (public)  

Venue：岩手県盛岡市   Country：Japan  

Venue：群馬県民会館、前橋商工会議所   Country：Japan  

Venue：福岡、九大医学部百年講堂   Country：Japan  

Venue：京都、国立京都国際会館   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：Sarasota   Country：United States  

Presentation type：Symposium, workshop panel (public)  

Venue：Sarasota   Country：United States  

Presentation type：Symposium, workshop panel (public)  

Venue：Sarasota   Country：United States  

Presentation type：Symposium, workshop panel (public)  

Venue：Sarasota   Country：United States  

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：札幌   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：札幌   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：札幌   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：札幌   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：Fukuoka   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：富山   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：富山   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：富山   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：Fukuoka   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：Sarasota   Country：United States  

Presentation type：Symposium, workshop panel (public)  

Venue：Kyoto   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：旭川   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：旭川   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：旭川   Country：Japan  

Presentation type：Oral presentation (invited, special)  

Venue：旭川   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：Nagoya   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：新潟   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：新潟   Country：Japan  

Presentation type：Oral presentation (invited, special)  

Venue：新潟   Country：Japan  

Presentation type：Oral presentation (invited, special)  

Venue：福岡   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：盛岡   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：盛岡   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：船堀   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：岐阜   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：金沢   Country：Japan  

Presentation type：Symposium, workshop panel (public)  

Venue：金沢   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：岡崎   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：埼玉   Country：Japan  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Others  

© 2017 Japanese Association for Oral Biology Background Gymnemic acids, triterpene glycosides, are known to act as human-specific sweet inhibitors. The long-lasting effect of gymnemic acids is diminished by γ-cyclodextrin. Here, we focus on the molecular mechanisms underlying the interaction between gymnemic acids and sweet taste receptor and/or γ-cyclodextrin by a sweet taste receptor assay in transiently transfected HEK293 cells. Highlight Application of gymnemic acids inhibited intracellular calcium responses to sweet compounds in HEK293 cells expressing human TAS1R2+TAS1R3 but not in those expressing the mouse sweet receptor Tas1r2+Tas1r3 after application of gymnemic acids. The effect of gymnemic acids was reduced after rinsing cells with γ-cyclodextrin. Based on species-specific sensitivities to gymnemic acids, we showed that the transmembrane domain of hTAS1R3 is involved in the sensitivity to gymnemic acids. Point mutation analysis in the transmembrane domain of hTAS1R3 revealed that gymnemic acids shared the same binding pocket with another sweet inhibitor, lactisole. Sensitivity to sweet compounds was also reduced by mixtures of glucuronic acid, a common gymnemic acid. In our molecular models, gymnemic acids interacted with a binding site formed in the transmembrane domain of hTAS1R3. Conclusion Gymnemic acids inhibit sweet responses in humans through an interaction between the glucuronosyl group of gymnemic acids and the transmembrane domain of hTAS1R3. Our molecular model provides a foundation for the development of taste modifiers.

DOI： 10.1016/j.job.2017.05.004

Language：Others  

© 2014 Japanese Association for Dental Science. The sense of taste plays a major role in evaluating the quality of food components in the oral cavity. Sweet, salty, umami, sour and bitter taste are generally accepted as five basic taste qualities. Among them, salty taste is attractive to animals and influences sodium intake. Angiotensin II (ANG II) and aldosterone (ALDO, which is stimulated by ANG II) are key hormones that regulate sodium homeostasis and water balance. At the peripheral gustatory organs, it has been reported that ALDO increases the amiloride-sensitivity of the rat gustatory neural responses to NaCl in a time course of several hours. A recent study demonstrated that ANG II suppresses amiloride-sensitivity of the mouse gustatory and behavioral responses to NaCl via its receptor AT1 within an hour. Moreover, ANG II enhances sweet taste sensitivity without affecting umami, sour and bitter tastes. These results suggest that the reciprocal and sequential regulatory mechanisms by ANG II (as an acute suppressor) together with ALDO (as a slow enhancer) on the salt taste sensitivity may exist in peripheral taste organs, contribute to salt intake, and play an important role in sodium homeostasis. Furthermore, the linkage between salty and sweet taste modulations via the ANG II signaling may optimize sodium and calorie intakes.

DOI： 10.1016/j.jdsr.2014.09.005

Language：Others  

L-Glutamate and 5′-ribonucleotides are known to elicit a unique taste, "umami," that is distinct from the tastes of sweet, salt, sour and bitter. Recent progress in molecular biology has identified several umami receptor candidates, such as the heterodimer T1R1/T1R3, and brain-expressed and taste-expressed type 1 and 4 metabotropic glutamate receptors (brain- and taste-mGluR1 and mGluR4). This paper summarizes recent findings on the receptor system for umami taste. Most of the findings support the idea that multiple receptors exist for umami taste, at least in mice. The accumulating evidence indicates that the potential role of the signal mediated by the transduction pathway involving T1R1/T1R3 may be different from that mediated by the pathway involving mGluRs. The former signal occurs mainly in the anterior tongue, and plays a major role in preference behavior, whereas the latter occurs mainly in the posterior tongue, is active in mice lacking T1R3, Gα-gustducin, IP3R3 or TRPM5, and contributes to behavioral discrimination between umami and other taste compounds. In humans, unlike in mice, T1R1/T1R3 acts as an umami-specific receptor that can discriminate between umami and other tastes, and thus account for umami-linked preferences or discrimination. ©2009 The Pharmaceutical Society of Japan.

DOI： 10.1248/jhs.55.674

Language：Japanese  

Expression of leptin peceptors (Ob-rs) and STAT3 mRNA in the mouse taste buds

Language：Japanese  

Expression of receptors (Ob-Rb) and sweet suppressive effects of leptin in the mouse taste buds

Type：Competition, symposium, etc. 

Number of participants：1,000

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Number of participants：100

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：1

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Number of participants：500

Type：Scientific advice/Review 

Type：Peer review 

Proceedings of domestic conference Number of peer-reviewed papers：76

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Number of participants：1,000

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Number of participants：1,000

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Number of participants：100

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Number of participants：50

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Number of participants：120

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Number of participants：500

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Number of participants：100

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