Yuzo Ninomiya

Gunma University, Maebashi-shi, Gunma-ken, Japan

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Publications (169)548.96 Total impact

  • Keiko Yasumatsu, Tomohiro Manabe, Ryusuke Yoshida, Ken Iwatsuki, Hisayuki Uneyama, Chiro Takahashi, Yuzo Ninomiya
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    ABSTRACT: Umami taste is elicited by L-glutamate and some other amino acids and is thought to be initiated by G-protein-coupled receptors. Proposed umami receptors include heterodimers of taste receptor type 1, members 1 and 3 (T1R1+T1R3), and metabotropic glutamate receptors 1 and 4 (mGluR1 and mGluR4). Accumulated evidences support the involvement of T1R1 + T1R3 in umami responses in mice. However, little is known about in vivo function of mGluRs in umami taste. Here, we examined taste responses of the chorda tympani (CT) and the glossopharyngeal (GL) nerves in wild-type mice and mice genetically lacking mGluR4 (mGluR4-KO). Our results indicated that compared to wild-type mice, mGluR4-KO mice showed significantly smaller gustatory nerve responses to glutamate and L(+)-2-amino-4-phosphonobutyrate (L-AP4, an agonist for group III mGluR) in both the CT and GL nerves without affecting responses to other taste stimuli. Residual glutamate responses in mGluR4-KO mice were not affected by (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG, an antagonist for group III mGluR), but were suppressed by gurmarin (a T1R3 blocker) in the CT and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA, an antagonist for group I mGluR) in the CT and GL nerve. In wild-type mice, both quisqualic acid (an agonist for group I mGluR) and L-AP4 elicited gustatory nerve responses and these responses were suppressed by addition of AIDA and CPPG, respectively. Collectively, the present study provided functional evidences for the involvement of mGluR4 in umami taste responses in mice. The results also suggest that T1R1+T1R3 and mGluR1 are involved in umami taste responses in mice. Thus umami taste would be mediated by multiple receptors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    The Journal of Physiology 12/2014; · 4.38 Impact Factor
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    ABSTRACT: Detection of tastes is critical for animals. Sweet, umami and bitter taste are mediated by G-protein coupled receptors that are expressed in the taste receptor cells. TAS1Rs which belong to class C G-protein coupled receptors form heterodimeric complexes to function as sweet (TAS1R2 + TAS1R3) or umami (TAS1R1 + TAS1R3) taste receptors. Umami taste is also considered to be mediated by mGluRs. TAS2Rs belong to class A G-protein coupled receptors and are responsible for bitter taste. After activation of these receptors, their second messenger pathways leads to depolarization and intracellular calcium increase in taste receptor cells. Then, transmitter is released from taste receptor cells leading to activation of taste nerve fibers and taste information are sent to the central nervous system. Recent studies on heterologous expression system and molecular modeling leads to better understanding of binding site of TAS1Rs and TAS2Rs and molecular mechanisms for interaction between taste substances and these receptors. TAS1Rs and TAS2Rs have multiple and single binding sites for structurally diverse ligands, respectively. Sensitivities of these receptors are known to differ among individuals, strains, and species. In addition, some species abolish these receptors and signaling molecules. Here we focus on structure, function, signaling, polymorphism, and molecular evolution of the taste G-protein coupled receptors.
    Journal of Applied Statistics 09/2014; · 0.45 Impact Factor
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    ABSTRACT: 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 sweet-suppressing effect of gymnemic acids and interaction between gymnemic acids vs. sweet taste receptor and/or γ-CD. To investigate whether gymnemic acids directly interact with human 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 ug/ml) inhibited the [Ca2+]i responses to sweet compounds in HEK293 cells heterologously expressing hT1R2+hT1R3 but not in those expressing mouse 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 which 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.
    The Journal of biological chemistry. 07/2014;
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    ABSTRACT: We reported recently that the taste type 1 receptor 3 (T1R3), a subunit of the sweet taste receptor, functions as a cell-surface glucose-sensing receptor in pancreatic β-cells. In the present study, we investigated the expression of T1R3 in pancreatic islets. mRNA for T1R2 and T1R3 was detected in mouse pancreatic islets. Quantitatively, the mRNA expression level of T1R2 was less than 1% of that of T1R3. Immunohistochemically, T1R3 was abundantly expressed in mouse islets whereas T1R2 was barely detected. Most immunoreactive T1R3 was colocalized with insulin and almost all β-cells were positive for T1R3. In addition, T1R3 was expressed in some portion of α-cells. Immunoreactivity of T1R3 in β-cells was markedly reduced in fed mice compared to those in fasting mice. In contrast, mRNA for T1R3 was not different in islets of fasting and fed mice. Glucose-induced insulin-secretion was higher in islets obtained from fasting mice compared to those from fed mice. The expression of T1R3 was markedly reduced in islets of ob/ob mice compared to those of control mice. Similarly, the expression of T1R3 was reduced in islet of db/db mice. In addition, the expression of T1R3 was markedly reduced in β-cells of fatty diabetic rats and GK rats, models of obese and non-obese type 2 diabetes, respectively. These results indicate that T1R3 is expressed mainly in β-cells and the expression levels are different depending upon the nutritional and metabolic conditions.
    Endocrine Journal 06/2014; · 2.23 Impact Factor
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    ABSTRACT: The sweet taste receptor is expressed in the taste bud and is activated by numerous sweet molecules with diverse chemical structures. It is, however, not known whether these sweet agonists induce a similar cellular response in target cells. Using MIN6 cells, a pancreatic β-cell line expressing endogenous sweet taste receptor, we addressed this question by monitoring changes in cytoplasmic Ca(2+) ([Ca(2+)]i) and cAMP ([cAMP]i) induced by four sweet taste receptor agonists. Glycyrrhizin evoked sustained elevation of [Ca(2+)]i but [cAMP]i was not affected. Conversely, an artificial sweetener saccharin induced sustained elevation of [cAMP]i but did not increase [Ca(2+)]i. In contrast, sucralose and acesulfame K induced rapid and sustained increases in both [Ca(2+)]i and [cAMP]i. Although the latter two sweeteners increased [Ca(2+)]i and [cAMP]i, their actions were not identical: [Ca(2+)]i response to sucralose but not acesulfame K was inhibited by gurmarin, an antagonist of the sweet taste receptor which blocks the gustducin-dependent pathway. In addition, [Ca(2+)]i response to acesulfame K but not to sucralose was resistant to a Gq inhibitor. These results indicate that four types of sweeteners activate the sweet taste receptor differently and generate distinct patterns of intracellular signals. The sweet taste receptor has amazing multimodal functions producing multiple patterns of intracellular signals.
    Endocrine Journal 08/2013; · 2.23 Impact Factor
  • Shusuke Iwata, Ryusuke Yoshida, Yuzo Ninomiya
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    ABSTRACT: In the oral cavity, taste receptor cells dedicate to detecting chemical compounds in foodstuffs and transmitting their signals to gustatory nerve fibers. Heretofore, five taste qualities (sweet, umami, bitter, salty and sour) are generally accepted as basic tastes. Each of these may have a specific role in the detection of nutritious and poisonous substances; sweet for carbohydrate sources of calories, umami for protein and amino acid contents, bitter for harmful compounds, salty for minerals and sour for ripeness of fruits and spoiled foods. Recent studies have revealed molecular mechanisms for reception and transduction of these five basic tastes. Sweet, umami and bitter tastes are mediated by G-protein coupled receptors (GPCRs) and second-messenger signaling cascades. Salty and sour tastes are mediated by channel-type receptors. In addition to five basic tastes, taste receptor cells may have the ability to detect fat taste, which is elicited by fatty acids, and calcium taste, which is elicited by calcium. Taste compounds eliciting either fat taste or calcium taste may be detected by specific GPCRs expressed in taste receptor cells. This review will focus on transduction mechanisms and cellular characteristics responsible for each of basic tastes, fat taste and calcium taste.
    Current pharmaceutical design 07/2013; · 4.41 Impact Factor
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    ABSTRACT: There is mounting evidence that, in addition to texture and olfaction, taste plays a role in the detection of long chain fatty acids. Triglycerides, the main components of oils and dietary fat, are hydrolyzed in the mouth by a lingual lipase secreted from the von Ebner gland and the released free fatty acids are detected by the taste system. GPR40 and GPR120, two fatty acid responsive G-protein coupled receptors (GPCRs), are expressed in taste bud cells, and knockout mice lacking either of those receptors have blunted taste nerve responses to and reduced preference for fatty acids. Here we investigated whether activation of those GPCRs is sufficient to elicit fat taste and preference. Five non-fatty acid agonists of GPR40 and two non-fatty acid agonists of GPR120 activated the glossopharyngeal nerve of wild-type mice but not of knockout mice lacking the cognate receptor. In human subjects, two-alternative forced choice tests, triangle tests and sensory profiling showed that non fatty acid agonists of GPR40 dissolved in water are detected in sip and spit tests and elicit a taste similar to that of linoleic acid, whereas two-alternative forced choice tests showed that two agonists of GPR120 in water are not perceived fattier than water alone. Wild-type mice did not show any preference for five agonists of GPR40, two agonists of GPR120 and mixtures of both agonists over water in two bottle preference tests. Together these data indicate that GPR40 mediated taste perception is not sufficient to generate preference.
    Neuroscience 07/2013; · 3.12 Impact Factor
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    ABSTRACT: Understanding the mechanisms underlying gustatory detection of dietary sodium is important for the prevention and treatment of hypertension. Here, we show that Angiotensin II (AngII), a major mediator of body fluid and sodium homeostasis, modulates salty and sweet taste sensitivities, and that this modulation critically influences ingestive behaviors in mice. Gustatory nerve recording demonstrated that AngII suppressed amiloride-sensitive taste responses to NaCl. Surprisingly, AngII also enhanced nerve responses to sweeteners, but had no effect on responses to KCl, sour, bitter, or umami tastants. These effects of AngII on nerve responses were blocked by the angiotensin II type 1 receptor (AT1) antagonist CV11974. In behavioral tests, CV11974 treatment reduced the stimulated high licking rate to NaCl and sweeteners in water-restricted mice with elevated plasma AngII levels. In taste cells AT1 proteins were coexpressed with αENaC (epithelial sodium channel α-subunit, an amiloride-sensitive salt taste receptor) or T1r3 (a sweet taste receptor component). These results suggest that the taste organ is a peripheral target of AngII. The specific reduction of amiloride-sensitive salt taste sensitivity by AngII may contribute to increased sodium intake. Furthermore, AngII may contribute to increased energy intake by enhancing sweet responses. The linkage between salty and sweet preferences via AngII signaling may optimize sodium and calorie intakes.
    Journal of Neuroscience 04/2013; 33(15):6267-77. · 6.91 Impact Factor
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    ABSTRACT: The T1R1 receptor subunit acts as umami taste receptor in combination with its partner T1R3. In addition, metabotropic glutamate receptors (brain- and taste- mGluR1 and mGluR4) are thought to function as umami taste receptors. To elucidate T1R1 function and the contribution of mGluRs to umami taste detection in vivo, we used newly developed knock-out (KO, T1R1-/-) mice, which lack the entire coding region of the Tas1r1 gene and express mCherry in T1R1-expressing cells. Gustatory nerve recordings demonstrated that T1R1-/- mice exhibited serious deficit in inosine monophosphate-elicited synergy but substantial residual responses to glutamate alone in both chorda tympani (CT) and glossopharyngeal (GL) nerves. Interestingly, CT nerve responses to sweeteners were smaller in T1R1-/- mice. Taste cell recordings demonstrated that many mCherry-expressing taste cells in T1R1+/- mice responded to sweet and umami compounds whereas those in T1R1-/- mice responded to sweet stimuli. The proportion of sweet-responsive cells was smaller in T1R1-/- than in T1R1+/- mice. Single cell RT-PCR demonstrated that some single mCherry-expressing cells expressed all three T1R subunits. CT and GL responses to glutamate were significantly inhibited by addition of mGluR antagonists in both T1R1-/- and T1R1+/- mice. Conditioned taste aversion tests demonstrated that both T1R1-/- and T1R1+/- mice were equally capable of discriminating glutamate from other basic taste stimuli. Avoidance conditioned to glutamate was significantly reduced by addition of mGluR antagonists. These results suggest that T1R1-expressing cells mainly contribute to umami taste synergism and partially to sweet sensitivity and that mGluRs are involved in the detection of umami compounds.
    The Journal of Physiology 01/2013; · 4.38 Impact Factor
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    ABSTRACT: Cholecystokinin (CCK) is secreted by endocrine cells of the proximal intestine in response to dietary components, including amino acids. CCK plays a variety of roles in digestive processes, including inhibition of food intake consistent with a role in satiety. In the lingual epithelium, the sensing of a broad spectrum of L-amino acids is accomplished by the T1R1-T1R3 heteromeric amino acid (umami) taste receptor. T1R1 and T1R3 subunits are also expressed in the intestine. A defining characteristic of umami sensing by T1R1-T1R3 is its potentiation by inosine or guanosine 5'-monophosphates (IMP/GMP). Furthermore, the T1R1-T1R3 receptor is not activated by tryptophan (TRP). We show here that, in response to L-amino acids (but not D-), phenylalanine (PHE), leucine (LEU), glutamate (GLUT) and TRP, STC-1 enteroendocrine cells and mouse proximal small intestinal tissue explants secrete CCK, and that IMP enhances PHE, LEU and GLUT-induced CCK release, but not TRP-induced CCK secretion. Furthermore, small interfering RNA (siRNA) inhibition of T1R1 expression, in STC-1 cells, results in significant diminution of PHE, LEU and GLUT-stimulated CCK release, but not TRP. In STC-1 cells and mouse intestine, gurmarin inhibits PHE, LEU and GLUT-induced CCK release but not TRP-stimulated CCK secretion. In contrast the CaSR antagonist, NPS2143, inhibits PHE-stimulated CCK release partially and TRP-induced CCK secretion totally in mouse intestine. However, NPS2143 has no effect on LEU- or GLUT-induced CCK secretion. Collectively, our data demonstrate that functional characteristics and cellular location of the gut-expressed T1R1-T1R3 support its role as a luminal sensor for PHE-, LEU-, and GLUT-induced CCK secretion.
    AJP Gastrointestinal and Liver Physiology 11/2012; · 3.65 Impact Factor
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    ABSTRACT: Nordihydroguaiaretic acid (NDGA) is known to have prominent anticancer activity against several cancers, and is also known to be an inhibitor of 5-lipoxygenase (5-LO). In this study, we investigated the regulatory function of NDGA on inflammatory bone destruction mediated by osteoclasts. NDGA markedly inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced formation of osteoclasts in cultures of murine osteoclast precursor cell line RAW-D cells and primary bone marrow-derived macrophages culture systems. The inhibitory effect of NDGA on osteoclastogenesis did not arise from the inhibition of 5-LO activity. NDGA did not affect MAPKs, such as p38, JNK, and NF-κB, but significantly inhibited the induction of NFATc1, a key transcription factor for osteoclastogenesis. NDGA also suppressed activation of ERK in osteoclast precursors. RANKL-induced calcium oscillation observed in osteoclast precursors was completely diminished by the addition of NDGA. In mature osteoclasts, RANKL-induced nuclear translocation of NFATc1 was clearly inhibited by NDGA treatment. Finally, in vivo studies demonstrated that administration of NDGA significantly reduced severe bone destruction and osteoclast recruitment in the ankle joint of rats with adjuvant-induced arthritis. These results indicate the potential utility of NDGA as a therapeutic agent for ameliorating inflammatory bone destruction in rheumatoid arthritis.Laboratory Investigation advance online publication, 8 October 2012; doi:10.1038/labinvest.2012.134.
    Laboratory Investigation 10/2012; · 3.96 Impact Factor
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    ABSTRACT: 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 (CB(1)) 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 CB(1) 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.
    Seminars in Cell and Developmental Biology 08/2012; · 6.20 Impact Factor
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    ABSTRACT: Amino acids are known to elicit complex taste, but most human psychophysical studies on the taste of amino acids have focused on a single basic taste, such as umami (savory) taste, sweetness, or bitterness. In this study, we addressed the potential relationship between the structure and the taste properties of amino acids by measuring the human gustatory intensity and quality in response to aqueous solutions of proteogenic amino acids in comparison to D: -enantiomers. Trained subjects tasted aqueous solution of each amino acid and evaluated the intensities of total taste and each basic taste using a category-ratio scale. Each basic taste of amino acids showed the dependency on its hydrophobicity, size, charge, functional groups on the side chain, and chirality of the alpha carbon. In addition, the overall taste of amino acid was found to be the combination of basic tastes according to the partial structure. For example, hydrophilic non-charged middle-sized amino acids elicited sweetness, and L: -enantiomeric hydrophilic middle-sized structure was necessary for umami taste. For example, L: -serine had mainly sweet and minor umami taste, and D: -serine was sweet. We further applied Stevens' psychophysical function to relate the total-taste intensity and the concentration, and found that the slope values depended on the major quality of taste (e.g., bitter large, sour small).
    Amino Acids 05/2012; · 3.91 Impact Factor
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    ABSTRACT: The heteromeric sweet taste receptor T1R2-T1R3 is expressed on the luminal membrane of certain populations of enteroendocrine cells. Sensing of sugars and other sweet compounds by this receptor activates a pathway in enteroendocrine cells, resulting in secretion of a number of gut hormones, including glucagon-like peptide 2 (GLP-2). This subsequently leads to upregulation in the expression of intestinal Na(+)/glucose cotransporter, SGLT1, and increased intestinal glucose absorption. On the basis of the current information available on the horse genome sequence, it has been proposed that the gene for T1R2 (Tas1R2) is absent in the horse. We show here, however, that horses express both the mRNA and protein for T1R2. Equine T1R2 is most closely homologous to that in the pig and the cow. T1R2 protein, along with T1R3, α-gustducin, and GLP-2 proteins are coexpressed in equine intestinal endocrine cells. Intravenous administration of GLP-2, in rats and pigs, leads to an increase in the expression of SGLT1 in absorptive enterocytes and enhancement in blood glucose concentrations. GLP-2 receptor is expressed in enteric neurons, excluding the direct effect of GLP-2 on enterocytes. However, electric stimulation of enteric neurons generates a neural response leading to SGLT1 upregulation, suggesting that sugar in the intestine activates a reflex increase in the functional expression of SGLT1. Horses possess the ability to upregulate SGLT1 expression in response to increased dietary carbohydrates, and to enhance the capacity of the gut to absorb glucose. The gut sweet receptor provides an accessible target for manipulating the equine gut to absorb glucose (and water), allowing greater energy uptake and hydration for hard-working horses.
    AJP Regulatory Integrative and Comparative Physiology 05/2012; 303(2):R199-208. · 3.28 Impact Factor
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    ABSTRACT: It remains unclear how the cerebral cortex of humans perceives taste temporally, and whether or not such objective data about the brain show a correlation with the current widely used conventional methods of taste-intensity sensory evaluation. The aim of this study was to investigate the difference in the time-intensity profile between salty and sweet tastes in the human brain. The time-intensity profiles of functional MRI (fMRI) data of the human taste cortex were analyzed using finite impulse response analysis for a direct interpretation in terms of the peristimulus time signal. Also, time-intensity sensory evaluations for tastes were performed under the same condition as fMRI to confirm the reliability of the temporal profile in the fMRI data. The time-intensity profile for the brain activations due to a salty taste changed more rapidly than those due to a sweet taste in the human brain cortex and was also similar to the time-intensity sensory evaluation, confirming the reliability of the temporal profile of the fMRI data. In conclusion, the time-intensity profile using finite impulse response analysis for fMRI data showed that there was a temporal difference in the neural responses between salty and sweet tastes over a given period of time. This indicates that there might be taste-specific temporal profiles of activations in the human brain.
    Neuroreport 03/2012; 23(6):400-4. · 1.40 Impact Factor
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    ABSTRACT: To clarify the regional differences in the expression and functional significance of Gα-gustducin in soft palate (SP) and fungiform (FF) taste buds, we examined the coexpression of Gα-gustducin with taste receptors and the impact of Gα-gustducin knockout (gKO) on neural responses to several sweet and bitter compounds. Sweet responses from both the greater superficial petrosal (GSP) and chorda tympani (CT) nerves in gKO mice were markedly depleted, reflecting overlapping expression of Gα-gustducin and Tas1r2. However, although Gα-gustducin was expressed in 87% and 88% of Tas2rs cells in the SP and FF, respectively, there were no statistically significant differences in the CT responses to quinine-HCl (QHCl) and denatonium (Den) between gKO and wild-type (WT) mice. In contrast, GSP responses to these compounds were markedly reduced in gKO mice with an apparent elevation of thresholds (>10-fold). These results suggest that 1) Gα-gustducin plays a critical role in sweet transduction in both the SP and the FF, 2) other Gα subunits coexpressed with Gα-gustducin in the FF are sufficient for responses to QHCl and Den, and 3) robust GSP responses to QHCl and Den occur in the SP by a Gα-gustducin-dependent mechanism, which is absent in the FF.
    Chemical Senses 03/2012; 37(3):241-51. · 3.22 Impact Factor
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    ABSTRACT: Mice lacking both the P2X2 and the P2X3 purinergic receptors (P2X-dblKO) exhibit loss of responses to all taste qualities in the taste nerves innervating the tongue. Similarly, these mice exhibit a near total loss of taste-related behaviors in brief access tests except for a near-normal avoidance of acidic stimuli. This persistent avoidance of acids despite the loss of gustatory neural responses to sour was postulated to be due to continued responsiveness of the superior laryngeal (SL) nerve. However, chemoresponses of the larynx are attributable both to taste buds and to free nerve endings. In order to test whether the SL nerve of P2X-dblKO mice remains responsive to acids but not to other tastants, we recorded responses from the SL nerve in wild-type (WT) and P2X-dblKO mice. WT mice showed substantial SL responses to monosodium glutamate, sucrose, urea, and denatonium-all of which were essentially absent in P2X-dblKO animals. In contrast, the SL nerve of P2X-dblKO mice exhibited near-normal responses to citric acid (50 mM) although responsiveness of both the chorda tympani and the glossopharyngeal nerves to this stimulus were absent or greatly reduced. These results are consistent with the hypothesis that the residual avoidance of acidic solutions by P2X-dblKO mice may be attributable to the direct chemosensitivity of nerve fibers innervating the laryngeal epithelium and not to taste.
    Chemical Senses 02/2012; 37(6):523-32. · 3.22 Impact Factor
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    ABSTRACT: Recent molecular studies have identified many candidate receptors for umami, typically the taste of monosodium glutamate (MSG). The candidate receptors, including taste-mGluR4, T1R1+T1R3, and truncated mGluR1, respond to MSG in the millimolar concentration range. Expression of brain-expressed mGluR4 and mGluR1 with much higher sensitivities to glutamate has also been reported in taste papillae. To test the involvement of brain-expressed mGluRs in umami taste, we tested glutamate agonists and antagonists at concentration ranges relevant to both types of the receptors using a combination of a detection threshold and conditioned taste aversion (CTA) methods in mice. The detection threshold experiment showed that mice could detect the group III mGluR agonist L(+)-2-amino-4-phosphonobutyrate (L-AP4) taste thresholds at 0.0009-0.0019 mM. Mice conditioned using CTA methods to avoid either MSG or MPG showed aversive responses to MSG with and without amiloride or to MPG, respectively, at concentrations of 0.0001 mM and above. A CTA to L-AP4 or MSG showed comparable concentration-response ranges for L-AP4 and MSG. The Group III mGluR antagonist, (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG), and the mGluR1 antagonist, 1-aminoindan-1,5-dicarboxylic acid (AIDA), suppressed aversive responses to glutamate agonists at concentrations between 0.0001 and 100mM in the CTA experiments. Our results suggest the possibility that brain-expressed mGluR4 and mGluR1 may contribute to umami taste in mice.
    Physiology & Behavior 02/2012; 105(3):709-19. · 3.16 Impact Factor
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    ABSTRACT: 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.
    The Journal of Physiology 12/2011; 590(Pt 5):1155-70. · 4.38 Impact Factor
  • Neuroscience Research 09/2011; 71. · 2.20 Impact Factor

Publication Stats

4k Citations
548.96 Total Impact Points

Institutions

  • 2009–2013
    • Gunma University
      • Institute for Molecular and Cellular Regulation
      Maebashi-shi, Gunma-ken, Japan
  • 2000–2013
    • Kyushu University
      • • Graduate School of Dental Science
      • • Faculty of Dental Science
      Fukuoka-shi, Fukuoka-ken, Japan
  • 1996–2013
    • Monell Chemical Senses Center
      Philadelphia, Pennsylvania, United States
  • 2012
    • University of Liverpool
      • Functional and Comparative Genomics
      Liverpool, ENG, United Kingdom
  • 1987–2012
    • Asahi University
      Gihu, Gifu, Japan
  • 2010
    • Karolinska Institutet
      • The Rolf Luft Research Center for Diabetes and Endocrinology
      Stockholm, Stockholm, Sweden
  • 2003–2007
    • Mount Sinai School of Medicine
      • Department of Neuroscience
      Manhattan, NY, United States
    • National Research Institute of Fisheries Science, Fisheries Research Agency
      Yokohama, Kanagawa, Japan
  • 2005
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
  • 2002–2005
    • National Food Research Institute
      Ibaragi, Ōsaka, Japan
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany
  • 2000–2005
    • Tokyo Medical and Dental University
      • Department of Fundamental Oral Health Care Sciences
      Edo, Tōkyō, Japan
  • 2001
    • Tottori University
      • Department of Physiology
      Tottori, Tottori-ken, Japan
  • 1991–1997
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States