start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=1 article-no= start-page=16 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sugar signals from oral glucose transporters elicit cephalic-phase insulin release in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cephalic-phase insulin release (CPIR) occurs before blood glucose increases after a meal. Although glucose is the most plausible cue to induce CPIR, peripheral sensory systems involved are not fully elucidated. We therefore examined roles of sweet sensing by a T1R3-dependent taste receptor and sugar sensing by oral glucose transporters in the oropharyngeal region in inducing CPIR. Spontaneous oral ingestion of glucose significantly increased plasma insulin 5 min later in wild-type (C57BL/6) and T1R3-knockout mice, but intragastric infusion did not. Oral treatment of glucose transporter inhibitors phlorizin and phloretin significantly reduced CPIR after spontaneous oral ingestion. In addition, a rapid increase in plasma insulin was significantly smaller in WT mice with spontaneous oral ingestion of nonmetabolizable glucose analog than in WT mice with spontaneous oral ingestion of glucose. Taken together, the T1R3-dependent receptor is not required for CPIR, but oral glucose transporters greatly contribute to induction of CPIR by sugars. en-copyright= kn-copyright= en-aut-name=TakamoriMitsuhito en-aut-sei=Takamori en-aut-mei=Mitsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgusaMasahiko en-aut-sei=Egusa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=The Center for Special Needs Dentistry, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Graduate School of Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cephalic-phase insulin response kn-keyword=Cephalic-phase insulin response en-keyword=Glucose transporters kn-keyword=Glucose transporters en-keyword=Glucose kn-keyword=Glucose en-keyword=Sweet taste receptor kn-keyword=Sweet taste receptor en-keyword=Food intake kn-keyword=Food intake END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=13 article-no= start-page=2941 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230628 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adrenomedullin Enhances Mouse Gustatory Nerve Responses to Sugars via T1R-Independent Sweet Taste Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=On the tongue, the T1R-independent pathway (comprising glucose transporters, including sodium-glucose cotransporter (SGLT1) and the K-ATP channel) detects only sugars, whereas the T1R-dependent (T1R2/T1R3) pathway can broadly sense various sweeteners. Cephalic-phase insulin release, a rapid release of insulin induced by sensory signals in the head after food-related stimuli, reportedly depends on the T1R-independent pathway, and the competitive sweet taste modulators leptin and endocannabinoids may function on these two different sweet taste pathways independently, suggesting independent roles of two oral sugar-detecting pathways in food intake. Here, we examined the effect of adrenomedullin (ADM), a multifunctional regulatory peptide, on sugar sensing in mice since it affects the expression of SGLT1 in rat enterocytes. We found that ADM receptor components were expressed in T1R3-positive taste cells. Analyses of chorda tympani (CT) nerve responses revealed that ADM enhanced responses to sugars but not to artificial sweeteners and other tastants. Moreover, ADM increased the apical uptake of a fluorescent D-glucose derivative into taste cells and SGLT1 mRNA expression in taste buds. These results suggest that the T1R-independent sweet taste pathway in mouse taste cells is a peripheral target of ADM, and the specific enhancement of gustatory nerve responses to sugars by ADM may contribute to caloric sensing and food intake. en-copyright= kn-copyright= en-aut-name=IwataShusuke en-aut-sei=Iwata en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaiShingo en-aut-sei=Takai en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SanematsuKeisuke en-aut-sei=Sanematsu en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigemuraNoriatsu en-aut-sei=Shigemura en-aut-mei=Noriatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NinomiyaYuzo en-aut-sei=Ninomiya en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University kn-affil= affil-num=4 en-affil=Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University kn-affil= affil-num=5 en-affil=Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=taste kn-keyword=taste en-keyword=sweet taste kn-keyword=sweet taste en-keyword=taste receptor family 1 members 2 and 3 kn-keyword=taste receptor family 1 members 2 and 3 en-keyword=sodium-glucose cotransporter 1 kn-keyword=sodium-glucose cotransporter 1 en-keyword=adrenomedullin kn-keyword=adrenomedullin en-keyword=caloric sensing kn-keyword=caloric sensing END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=6 article-no= start-page=1150 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Taste Responses and Ingestive Behaviors to Ingredients of Fermented Milk in Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fermented milk is consumed worldwide because of its nutritious and healthful qualities. Although it is somewhat sour, causing some to dislike it, few studies have examined taste aspects of its ingredients. Wild-type mice and T1R3-GFP-KO mice lacking sweet/umami receptors were tested with various taste components (sucrose, galactose, lactose, galacto-oligosaccharides, fructo-oligosaccharides, l- and d-lactic acid) using 48 h two-bottle tests and short-term lick tests. d-lactic acid levels were measured after the ingestion of d- or; l-lactic acid or water to evaluate d-lactic acidosis. In wild-type mice, for the sweet ingredients the number of licks increased in a concentration-dependent manner, but avoidance was observed at higher concentrations in 48 h two-bottle tests; the sour ingredients d- and l-lactic acid showed concentration-dependent decreases in preference in both short- and long-term tests. In 48 h two-bottle tests comparing d- and l-lactic acid, wild-type but not T1R3-GFP-KO mice showed higher drinking rates for l-lactic acid. d-lactic acidosis did not occur and thus did not contribute to this preference. These results suggest that intake in short-term lick tests varied by preference for each ingredient, whereas intake variation in long-term lick tests reflects postingestive effects. l-lactic acid may have some palatable taste in addition to sour taste. en-copyright= kn-copyright= en-aut-name=YamaseYuko en-aut-sei=Yamase en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuangHai en-aut-sei=Huang en-aut-mei=Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgusaMasahiko en-aut-sei=Egusa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=postingestive effects kn-keyword=postingestive effects en-keyword=galactose kn-keyword=galactose en-keyword=lactose kn-keyword=lactose en-keyword=oligosaccharides kn-keyword=oligosaccharides en-keyword=lactic acid kn-keyword=lactic acid END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=57 end-page=63 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The sweet taste receptor, glucose transporters, and the ATP-sensitive K+ (KATP) channel: sugar sensing for the regulation of energy homeostasis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sugar detection in the oral cavity does not solely depend on the TAS1R2 + TAS1R3 sweet receptor. Similar to gut, pancreas, and hypothalamic neurons, in the tongue glucose transporters and ATP-sensitive K+ (KATP) channels are also involved in sugar detection. Among them, the KATP channel is the target for the antiobesity hormone leptin, which inhibits sugar-sensitive cells such as sweet taste cells, pancreatic β-cells, and hypothalamic orexigenic neurons. Sugar signals from the taste organ elicit cephalic-phase insulin release, and those from the gut contribute to sweet preference for caloric sugars. All of these systems are indispensable for maintaining energy homeostasis. Thus, an exquisite system for sugar detection/signaling to regulate energy homeostasis exists in our body. en-copyright= kn-copyright= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YasumatsuKeiko en-aut-sei=Yasumatsu en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaYuzo en-aut-sei=Ninomiya en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Tokyo Dental Junior College kn-affil= affil-num=3 en-affil=Division of Sensory Physiology and Medical Application Sensing, Research and Development Center for Five-Sense Devices, Kyushu University kn-affil= en-keyword=gustatory nerve fibers kn-keyword=gustatory nerve fibers en-keyword=leptin kn-keyword=leptin en-keyword=cephalic-phase insulin release kn-keyword=cephalic-phase insulin release en-keyword=sweet taste kn-keyword=sweet taste en-keyword=food intake kn-keyword=food intake END start-ver=1.4 cd-journal=joma no-vol=158 cd-vols= no-issue= article-no= start-page=233 end-page=245 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phosphatidylinositol‐3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Leptin is known to selectively suppress neural and taste cell responses to sweet compounds. The sweet suppressive effect of leptin is mediated by the leptin receptor Ob‐Rb, and the ATP‐gated K+ (KATP) channel expressed in some sweet‐sensitive, taste receptor family 1 member 3 (T1R3)‐positive taste cells. However, the intracellular transduction pathway connecting Ob‐Rb to KATP channel remains unknown. Here we report that phosphoinositide 3‐kinase (PI3K) mediates leptin's suppression of sweet responses in T1R3‐positive taste cells. In in situ taste cell recording, systemically administrated leptin suppressed taste cell responses to sucrose in T1R3‐positive taste cells. Such leptin's suppression of sucrose responses was impaired by co‐administration of PI3K inhibitors (wortmannin or LY294002). In contrast, co‐administration of signal transducer and activator of transcription 3 inhibitor (Stattic) or Src homology region 2 domain‐containing phosphatase‐2 inhibitor (SHP099) had no effect on leptin's suppression of sucrose responses, although signal transducer and activator of transcription 3 and Src homology region 2 domain‐containing phosphatase‐2 were expressed in T1R3‐positive taste cells. In peeled tongue epithelium, phosphatidylinositol (3,4,5)‐trisphosphate production and phosphorylation of AKT by leptin were immunohistochemically detected in some T1R3‐positive taste cells but not in glutamate decarboxylase 67‐positive taste cells. Leptin‐induced phosphatidylinositol (3,4,5)‐trisphosphate production was suppressed by LY294002. Thus, leptin suppresses sweet responses of T1R3‐positive taste cells by activation of Ob‐Rb–PI3K–KATP channel pathway. en-copyright= kn-copyright= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MargolskeeRobert F. en-aut-sei=Margolskee en-aut-mei=Robert F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaYuzo en-aut-sei=Ninomiya en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Monell Chemical Senses Center kn-affil= affil-num=3 en-affil=Monell Chemical Senses Center kn-affil= en-keyword=energy homeostasis kn-keyword=energy homeostasis en-keyword=leptin signaling kn-keyword=leptin signaling en-keyword=metabolic sensor kn-keyword=metabolic sensor en-keyword=obesity kn-keyword=obesity en-keyword=sweet receptor cell kn-keyword=sweet receptor cell END start-ver=1.4 cd-journal=joma no-vol=228 cd-vols= no-issue= article-no= start-page=102712 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202011 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Orexin A and B in the rat superior salivatory nucleus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Orexin (OX), which regulates sleep and wakefulness and feeding behaviors has 2 isoforms, orexin-A and -B (OXA and OXB). In this study, the distribution of OXA and OXB was examined in the rat superior salivatory nucleus (SSN) using retrograde tracing and immunohistochemical and methods. OXA- and OXB-immunoreactive (-ir) nerve fibers were seen throughout the SSN. These nerve fibers surrounded SSN neurons retrogradely labeled with Fast blue (FB) from the corda-lingual nerve. FB-positive neurons had pericellular OXA- (47.5%) and OXB-ir (49.0%) nerve fibers. Immunohistochemistry for OX receptors also demonstrated the presence of OX1R and OX2R in FB-positive SSN neurons. The majority of FB-positive SSN neurons contained OX1R- (69.7%) or OX2R-immunoreactivity (57.8%). These neurons had small and medium-sized cell bodies. In addition, half of FB-positive SSN neurons which were immunoreactive for OX1R (47.0%) and OX2R (52.2%) had pericellular OXA- and OXB-ir nerve fibers, respectively. Co-expression of OX1R- and OX2R was common in FB-positive SSN neurons. The present study suggests a possibility that OXs regulate the activity of SSN neurons through OX receptors. en-copyright= kn-copyright= en-aut-name=SatoTadasu en-aut-sei=Sato en-aut-mei=Tadasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YajimaTakehiro en-aut-sei=Yajima en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujitaMasako en-aut-sei=Fujita en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobashiMotoi en-aut-sei=Kobashi en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IchikawaHiroyuki en-aut-sei=Ichikawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Oral and Craniofacial Anatomy, Tohoku University Graduate School of Dentistry kn-affil= affil-num=2 en-affil=Division of Oral and Craniofacial Anatomy, Tohoku University Graduate School of Dentistry kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Oral and Craniofacial Anatomy, Tohoku University Graduate School of Dentistry kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Orexin kn-keyword=Orexin en-keyword=Orexin receptor kn-keyword=Orexin receptor en-keyword=Superior salivatory nucleus kn-keyword=Superior salivatory nucleus en-keyword=Preganglionic neuron kn-keyword=Preganglionic neuron en-keyword=Chorda-lingual nerve kn-keyword=Chorda-lingual nerve en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=12 article-no= start-page=4422 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200622 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague-Dawley rats under urethane-chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested. en-copyright= kn-copyright= en-aut-name=KobashiMotoi en-aut-sei=Kobashi en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimataniYuichi en-aut-sei=Shimatani en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujitaMasako en-aut-sei=Fujita en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsuoRyuji en-aut-sei=Matsuo en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Engineering, Faculty of Science and Engineering, Tokyo City University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=GLP-1 kn-keyword=GLP-1 en-keyword=orexin kn-keyword=orexin en-keyword=SB334867 kn-keyword=SB334867 en-keyword=swallowing kn-keyword=swallowing en-keyword=NTS kn-keyword=NTS en-keyword=rats kn-keyword=rats END start-ver=1.4 cd-journal=joma no-vol=369 cd-vols= no-issue= article-no= start-page=29 end-page=39 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20180115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bitter Taste Responses of Gustducin-positive Taste Cells in Mouse Fungiform and Circumvallate Papillae en-subtitle= kn-subtitle= en-abstract= kn-abstract= 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. en-copyright= kn-copyright= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakaiShingo en-aut-sei=Takai en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SanematsuKeisuke en-aut-sei=Sanematsu en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MargolskeeRobert F. en-aut-sei=Margolskee en-aut-mei=Robert F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigemuraNoriatsu en-aut-sei=Shigemura en-aut-mei=Noriatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NinomiyaYuzo en-aut-sei=Ninomiya en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University kn-affil= affil-num=2 en-affil=Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University kn-affil= affil-num=3 en-affil=Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University kn-affil= affil-num=4 en-affil=Monell Chemical Senses Center kn-affil= affil-num=5 en-affil=Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University kn-affil= affil-num=6 en-affil=Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University kn-affil= en-keyword=bitter antagonists kn-keyword=bitter antagonists en-keyword=bitter receptor kn-keyword=bitter receptor en-keyword=breadth of responsiveness kn-keyword=breadth of responsiveness en-keyword=taste coding kn-keyword=taste coding en-keyword=transgenic mouse kn-keyword=transgenic mouse END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=135041 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Bitter Receptor Antagonists on Behavioral Lick Responses of Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract= 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. en-copyright= kn-copyright= en-aut-name=MasamotoMichimasa en-aut-sei=Masamoto en-aut-mei=Michimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobashiMotoi en-aut-sei=Kobashi en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShigemuraNoriatsu en-aut-sei=Shigemura en-aut-mei=Noriatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University kn-affil= affil-num=5 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bitter coding kn-keyword=bitter coding en-keyword=bitter inhibitor kn-keyword=bitter inhibitor en-keyword=gustatory response kn-keyword=gustatory response en-keyword=species difference kn-keyword=species difference en-keyword=taste perception kn-keyword=taste perception END