九州大学 研究者情報
論文一覧
髙井 信吾(たかい しんご) データ更新日:2021.06.29

助教 /  歯学研究院 歯学部門 口腔常態制御学講座 口腔機能解析学分野


原著論文
1. 髙井 信吾, 重村 憲徳, インスリンシグナルの末梢味覚器における役割 味細胞の機能調節から分化/増殖に対する影響まで, 化学と生物, Vol.59, No.3, 122-129, 2021.03.
2. Yu Yamada, Shingo Takai, Yu Watanabe, Ayana Osaki, Yuko Kawabata, Asami Oike, Ayaka Hirayama, Shusuke Iwata, Keisuke Sanematsu, Shoji Tabata, Noriatsu Shigemura, Gene expression profiling of α-gustducin-expressing taste cells in mouse fungiform and circumvallate papillae, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2021.04.022, 2021.06.
3. Ayana Osaki, Keisuke Sanematsu, Junichi Yamazoe, Fumie Hirose, Yu Watanabe, Yuko Kawabata, Asami Oike, Ayaka Hirayama, Yu Yamada, Shusuke Iwata, Shingo Takai, Naohisa Wada, Noriatsu Shigemura, Drinking Ice-Cold Water Reduces the Severity of Anticancer Drug-Induced Taste Dysfunction in Mice., International journal of molecular sciences, 10.3390/ijms21238958, 21, 23, 2020.11, 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..
4. Takai S, Shigemura N, Insulin function in peripheral taste organ homeostasis, Current Oral Health Reports, 10.1007/s40496-020-00266-2, 7, 168-173, 2020.03.
5. Fumie Hirose, Shingo Takai, Ichiro Takahashi, Noriatsu Shigemura, Expression of protocadherin-20 in mouse taste buds, Scientific Reports, 10.1038/s41598-020-58991-8, 10, 1, 2020.02, © 2020, The Author(s). 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..
6. Shingo Takai, Yu Watanabe, Keisuke Sanematsu, Ryusuke Yoshida, Robert F. Margolskee, Peihua Jiang, Ikiru Atsuta, Kiyoshi Koyano, Yuzo Ninomiya, Noriatsu Shigemura, Effects of insulin signaling on mouse taste cell proliferation, PloS one, 10.1371/journal.pone.0225190, 14, 11, 2019.11, [URL], 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..
7. 川端 由子, 高井 信吾, 吉田 竜介, 實松 敬介, 重村 憲徳, 抗不整脈薬フレカイニドがマウス味蕾オルガノイドおよび味行動応答に及ぼす影響, Journal of Oral Biosciences Supplement, 2019, 395-395, 2019.10.
8. Noriatsu Shigemura, Shingo Takai, Fumie Hirose, Ryusuke Yoshida, Keisuke Sanematsu, Yuzo Ninomiya, Expression of Renin-Angiotensin System Components in the Taste Organ of Mice, Nutrients, 10.3390/nu11092251, 11, 9, 2019.09, The systemic renin-angiotensin system (RAS) is an important regulator of body fluid and sodium homeostasis. Angiotensin II (AngII) is a key active product of the RAS. We previously revealed that circulating AngII suppresses amiloride-sensitive salt taste responses and enhances the responses to sweet compounds via the AngII type 1 receptor (AT1) expressed in taste cells. However, the molecular mechanisms underlying the modulation of taste function by AngII remain uncharacterized. Here we examined the expression of three RAS components, namely renin, angiotensinogen, and angiotensin-converting enzyme-1 (ACE1), in mouse taste tissues. We found that all three RAS components were present in the taste buds of fungiform and circumvallate papillae and co-expressed with αENaC (epithelial sodium channel α-subunit, a salt taste receptor) or T1R3 (taste receptor type 1 member 3, a sweet taste receptor component). Water-deprived mice exhibited significantly increased levels of renin expression in taste cells (p < 0.05). These results indicate the existence of a local RAS in the taste organ and suggest that taste function may be regulated by both locally-produced and circulating AngII. Such integrated modulation of peripheral taste sensitivity by AngII may play an important role in sodium/calorie homeostasis..
9. 吉田 竜介, 實松 敬介, 高井 信吾, 岩田 周介, 重村 憲徳, ヒト味覚認知閾値に対する低濃度塩添加の影響, 日本味と匂学会誌, 第53回大会Proceeding集, S35-S38, 2019.09.
10. 實松 敬介, 井上 真由子, 高井 信吾, 二ノ宮 裕三, 味覚嗅覚の調節因子と中枢機構に関する新展開 グルカゴン様ペプチド-1受容体遺伝子多型と甘味認知閾値との関連について, Journal of Oral Biosciences Supplement, 2018, 130-130, 2018.09.
11. 川端 由子, 高井 信吾, 吉田 竜介, 實松 敬介, 重村 憲徳, 味覚障害誘発薬剤がマウス味蕾オルガノイドへ与える影響, Journal of Oral Biosciences Supplement, 2018, 473-473, 2018.09.
12. Ryusuke Yoshida, Shingo Takai, Keisuke Sanematsu, Robert F. Margolskee, Noriatsu Shigemura, Yuzo Ninomiya, Bitter Taste Responses of Gustducin-positive Taste Cells in Mouse Fungiform and Circumvallate Papillae, Neuroscience, 10.1016/j.neuroscience.2017.10.047, 369, 29-39, 2018.01, © 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..
13. Ryusuke Yoshida, Misa Shin, Keiko Yasumatsu, Shingo Takai, Mayuko Inoue, Noriatsu Shigemura, Soichi Takiguchi, Seiji Nakamura, Yuzo Ninomiya, The role of cholecystokinin in peripheral taste signaling in mice, Frontiers in Physiology, 10.3389/fphys.2017.00866, 8, OCT, 866, 2017.10, © 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..
14. Shingo Takai, Ryusuke Yoshida, Noriatsu Shigemura, Yuzo Ninomiya, Peptide Signaling in Taste Transduction, Chemosensory Transduction: The Detection of Odors, Tastes, and Other Chemostimuli, 10.1016/B978-0-12-801694-7.00017-2, 299-317, 2016.02, © 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..
15. Shingo Takai, Ryusuke Yoshida, Keiko Yasumatsu, Noriatsu Shigemura, Yuzo Ninomiya, The function of glucagon-like peptide-1 in the mouse peripheral taste system, Journal of Oral Biosciences, 10.1016/j.job.2015.09.002, 58, 1, 10-15, 2016.02, © 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..
16. Shingo Takai, Keiko Yasumatsu, Mayuko Inoue, Shusuke Iwata, Ryusuke Yoshida, Noriatsu Shigemura, Yuchio Yanagawa, Daniel J. Drucker, Robert F. Margolskee, Yuzo Ninomiya, Glucagon-like peptide-1 is specifically involved in sweet taste transmission, FASEB Journal, 10.1096/fj.14-265355, 29, 6, 2268-2280, 2015.06, © 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..
17. 髙井 信吾, 中野 (安松) 啓子, 吉田 竜介, 重村 憲徳, 二ノ宮 裕三, 味神経に発現するGLP-1レセプターとその役割, 日本味と匂学会誌第21巻3号, 2015.02.
18. Keiko Yasumatsu, Yoko Ogiwara, Shingo Takai, Ryusuke Yoshida, Ken Iwatsuki, Kunio Torii, Robert F. Margolskee, Yuzo Ninomiya, Umami taste in mice uses multiple receptors and transduction pathways, Journal of Physiology, 10.1113/jphysiol.2011.211920, 590, 5, 1155-1170, 2012.02, The distinctive umami taste elicited by l-glutamate and some other amino acids is thought to be initiated by G-protein-coupled receptors. Proposed umami receptors include heteromers of taste receptor type 1, members 1 and 3 (T1R1+T1R3), and metabotropic glutamate receptors 1 and 4 (mGluR1 and mGluR4). Multiple lines of evidence support the involvement of T1R1+T1R3 in umami responses of mice. Although several studies suggest the involvement of receptors other than T1R1+T1R3 in umami, the identity of those receptors remains unclear. Here, we examined taste responsiveness of umami-sensitive chorda tympani nerve fibres from wild-type mice and mice genetically lacking T1R3 or its downstream transduction molecule, the ion channel TRPM5. Our results indicate that single umami-sensitive fibres in wild-type mice fall into two major groups: sucrose-best (S-type) and monopotassium glutamate (MPG)-best (M-type). Each fibre type has two subtypes; one shows synergism between MPG and inosine monophosphate (S1, M1) and the other shows no synergism (S2, M2). In both T1R3 and TRPM5 null mice, S1-type fibres were absent, whereas S2-, M1- and M2-types remained. Lingual application of mGluR antagonists selectively suppressed MPG responses of M1- and M2-type fibres. These data suggest the existence of multiple receptors and transduction pathways for umami responses in mice. Information initiated from T1R3-containing receptors may be mediated by a transduction pathway including TRPM5 and conveyed by sweet-best fibres, whereas umami information from mGluRs may be mediated by TRPM5-independent pathway(s) and conveyed by glutamate-best fibres. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society..
19. Mayu Niki, Shingo Takai, Yoko Kusuhara, Yuzo Ninomiya, Ryusuke Yoshida, Responses to apical and basolateral application of glutamate in mouse fungiform taste cells with action potentials., Cellular and molecular neurobiology, 10.1007/s10571-011-9702-5, 31, 7, 1033-1040, 2011.10, In taste bud cells, glutamate may elicit two types of responses, as an umami tastant and as a neurotransmitter. Glutamate applied to apical membrane of taste cells would elicit taste responses whereas glutamate applied to basolateral membrane may act as a neurotransmitter. Using restricted stimulation to apical or basolateral membrane of taste cells, we examined responses of taste cells to glutamate stimulation, separately. Apical application of monosodium glutamate (MSG, 0.3 M) increased firing frequency in some of mouse fungiform taste cells that evoked action potentials. These cells were tested with other basic taste compounds, NaCl (salty), saccharin (sweet), HCl (sour), and quinine (bitter). MSG-sensitive taste cells could be classified into sweet-best (S-type), MSG-best (M-type), and NaCl or other electrolytes-best (N- or E/H-type) cells. Furthermore, S- and M-type could be classified into two sub-types according to the synergistic effect between MSG and inosine-5'-monophosphate (S1, M1 with synergism; S2, M2 without synergism). Basolateral application of glutamate (100 μM) had almost no effect on the mean spontaneous firing rates in taste cells. However, about 10% of taste cells tested showed transient increases in spontaneous firing rates (>mean + 2 standard deviation) after basolateral application of glutamate. These results suggest the existence of multiple types of umami-sensitive taste cells and the existence of glutamate receptor(s) on the basolateral membrane of a subset of taste cells..
20. Mayu Niki, Ryusuke Yoshida, Shingo Takai, Yuzo Ninomiya, Gustatory signaling in the periphery
Detection, transmission, and modulation of taste information, Biological and Pharmaceutical Bulletin, 10.1248/bpb.33.1772, 33, 11, 1772-1777, 2010.11, [URL], Gustatory signaling begins with taste receptor cells that express taste receptors. Recent molecular biological studies have identified taste receptors and transduction components for basic tastes (sweet, salty, sour, bitter, and umami). Activation of these receptor systems leads to depolarization and an increase in [Ca2+]i in taste receptor cells. Then transmitters are released from taste cells and activate gustatory nerve fibers. The connection between taste cells and gustatory nerve fibers would be specific because there may be only limited divergence of taste information at the peripheral transmission. Recent studies have demonstrated that sweet taste information can be modulated by hormones or other endogenous factors that could act on their receptors in a specific group of taste cells. These peripheral modulations of taste information may influence preference behavior and food intake. This paper summarizes data on molecular mechanisms for detection and transduction of taste signals in taste bud cells, information transmission from taste cells to gustatory nerve fibers, and modulation of taste signals at peripheral taste organs, in particular for sweet taste, which may play important roles in regulating energy homeostasis..

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