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Yuzo Ninomiya

Publications and source records attributed to Yuzo Ninomiya.

29 records · Page 2Linked to original sources
PubMed2003

Regional expression patterns of taste receptors and gustducin in the mouse tongue.

In order to understand differences in taste sensitivities of taste bud cells between the anterior and posterior part of tongue, it is important to analyze the regional expression patterns of genes related to taste signal transduction on the tongue. Here we examined the expression pattern of a taste receptor family, the T1r family, and gustducin in circumvallate and fungiform papillae of the mouse tongue using double-labeled in situ hybridization. Each member of the T1r family was expressed in both circumvallate and fungiform papillae with some differences in their expression patterns. The most striking difference between fungiform and circumvallate papillae was observed in their co-expression patterns of T1r2, T1r3, and gustducin. T1r2-positive cells in fungiform papillae co-expressed T1r3 and gustducin, whereas T1r2 and T1r3 double-positive cells in circumvallate papillae merely expressed gustducin. These results suggested that in fungiform papillae, gustducin might play a role in the sweet taste signal transduction cascade mediated by a sweet receptor based on the T1r2 and T1r3 combination, in fungiform papillae.

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PubMed2003

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

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 strains tested. The db/db mice, however, had a RT-PCR product containing an abnormal db insertion that 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 ip injection of leptin in ob/ob and normal littermates, 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.

Animals↗
PubMed2003

Detection of sweet and umami taste in the absence of taste receptor T1r3.

The tastes of sugars (sweet) and glutamate (umami) are thought to be detected by T1r receptors expressed in taste cells. Molecular genetics and heterologous expression implicate T1r2 plus T1r3 as a sweet-responsive receptor,and T1r1 plus T1r3,as well as a truncated form of the type 4 metabotropic glutamate receptor (taste-mGluR4),as umami-responsive receptors. Here,we show that mice lacking T1r3 showed no preference for artificial sweeteners and had diminished but not abolished behavioral and nerve responses to sugars and umami compounds. These results indicate that T1r3-independent sweet- and umami-responsive receptors and/or pathways exist in taste cells.

Animals↗
PubMed2003

Recovery of amiloride-sensitive neural coding during regeneration of the gustatory nerve: behavioral-neural correlation of salt taste discrimination.

The chorda tympani (CT) nerve innervating the anterior tongue contains two types of NaCl-responsive fibers: one, the N-type, receives input from receptor cells, the NaCl responses of which are strongly inhibited by amiloride, whereas the other, the E-type, receives input from cells poorly sensitive or insensitive to amiloride. To investigate the formation of this differentially responsive neural system, we crushed the mouse CT nerve and examined the subsequent recovery of NaCl responses and amiloride sensitivity of the regenerated nerve and behavioral discrimination between NaCl and KCl. At 2 weeks after the nerve crush, no significant response of the nerve to chemical stimuli was observed. At 3 weeks, responses to salts gradually reappeared. In this period, almost all single fibers responding to NaCl were insensitive to amiloride (E-type). At 4 weeks, some of the single fibers showed amiloride sensitivity (N-type) and behavioral discrimination between NaCl and KCl reappeared. After >or=5 weeks, the number of N-type fibers had reached the control level and became approximately equal to that of E-type fibers. During the course of recovery, N-type and E-type fibers were clearly distinguishable on the basis of their amiloride sensitivities, their KCl/NaCl response ratios, and their concentration-response relationships to NaCl. These results suggest that two salt-responsive systems are independently reformed after the nerve crush. The selective synapse reformation may account for recovery of behavioral discrimination between NaCl and KCl after taste nerve crush and regeneration. It may also explain stable sensory coding for taste quality during the continuous turnover of receptor cells in the healthy animal.

Amiloride↗
PubMed2003

Conditioned taste aversion learning in leptin-receptor-deficient db/db mice.

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 (10 s) lick test and a long-term (48 h) 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.

Animals↗
PubMed2003

Co-expression pattern of Shh with Prox1 and that of Nkx2.2 with Mash1 in mouse taste bud.

In mammals, taste buds are maintained by continuous turnover of cells, even in adulthood. Cell proliferation and differentiation continue to produce taste cells, which express various genes related to taste reception. We found the co-expression of Sonic hedgehog (Shh) with Prox1 and that of Nkx2.2 with Mash1 in adult mouse taste buds. Whereas Prox1was expressed strongly in cells in the basal region of mouse taste buds where Shh was co-expressed, it was expressed weakly in almost all taste bud cells lacking Shh expression. At 0.5 day after birth, when taste cells have not yet differentiated, the expressions of Shh and Prox1 completely overlapped in the epithelium of circumvallate papillae. Nkx2.2 was observed in cells expressing Mash1, but not in cells expressing genes related to taste reception, such as gustducin and T1R3. Almost all fusiform cells expressing Mash1 co-expressed Nkx2.2, while the majority of round cells expressing Mash1 in the basal region of taste buds lacked Nkx2.2 expression.

Animals↗
PubMed2003

Gurmarin suppression of licking responses to sweetener-quinine mixtures in C57BL mice.

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 (QHCl) in water-deprived mice. Numbers of licks for sucrose mixed with 1 or 3 mM QHCl increased with increasing concentration of sucrose from 0.01 to 1.0 M. Oral infusion with 30 micro g/ml Gur produced significant decreases in responses to concentration series for sucrose mixed with 3 mM QHCl, whereas no such effect by Gur was observed in responses to QHCl alone or QHCl-mixed HCl, NaCl or monosodium glutamate. The Gur suppression of QHCl-mixed sucrose responses, which otherwise lasted for 2-3 h, rapidly returned to approximately 80% of control levels after oral infusion with beta-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.

Animals↗
PubMed2003

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

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.

Animals↗
PubMed2002

Leptin and sweet taste.

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.

Animals↗
PubMed2002

The neural differentiation gene Mash-1 has a distinct pattern of expression from the taste reception-related genes gustducin and T1R2 in the taste buds.

Taste bud cells have a limited lifespan and are continuously replaced just like other epithelial cells. Although there is some evidence that taste buds may arise from the local epithelium, taste receptor cells have neuronal properties. This implies that there must be a critical stage at which the epithelial precursor cells for taste receptor cells start to exhibit neural properties during the differentiation of the taste receptor cells. The expression of the neural-specific transcription factors Mash-1 and Prox-1 in the nervous system is transient and precedes neuronal differentiation. Therefore, we examined the expression of Mash-1 and Prox-1 in the epithelium of circumvallate papillae of the tongue in order to clarify the localization of the precursor cells with neural properties and observed that both expressions are restricted to the taste buds. Two-colour in situ hybridization showed that the signals for Mash-1 did not overlap those for taste receptor cell-specific genes such as gustducin and T1R2. In the process of development and regeneration of the taste buds, the expression of Mash-1 preceded that of gustducin and T1R2. These observations suggest that Mash-1 could be a candidate for a marker of immature taste receptor cells, including the cells that express gustducin and/or T1R2 at a later stage.

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