Chemical Senses Advance Access originally published online on June 2, 2005
Chemical Senses 2005 30(6):491-496; doi:10.1093/chemse/bji041
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mouse Strain Differences in Gurmarin-sensitivity of Sweet Taste Responses Are Not Associated with Polymorphisms of the Sweet Receptor Gene, Tas1r3
Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Correspondence to be sent to: Yuzo Ninomiya, Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. e-mail: nino{at}dent.kyushu-u.ac.jp
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Gurmarin (Gur) is a peptide that selectively inhibits responses of the chorda tympani (CT) nerve to sweet compounds in rodents. In mice, the sweet-suppressing effect of Gur differs among strains. The inhibitory effect of Gur is clearly observed in C57BL/6 mice, but only slightly, if at all, in BALB/c mice. These two mouse strains possess different alleles of the sweet receptor gene, Sac (Tas1r3) (taster genotype for C57BL/6 and non-taster genotype for BALB/c mice), suggesting that polymorphisms in the gene may account for differential sensitivity to Gur. To investigate this possibility, we examined the effect of Gur in another Tas1r3 non-taster strain, 129X1/Sv mice. The results indicated that unlike non-taster BALB/c mice but similar to taster C57BL/6 mice, 129X1/Sv mice exhibited significant inhibition of CT responses to various sweet compounds by Gur. This suggests that the mouse strain difference in the Gur inhibition of sweet responses of the CT nerve may not be associated with polymorphisms of Tas1r3.
Key words: chorda tympani nerve, gurmarin, mouse strain differences, polymorphisms, sweet taste, Tas1r3
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Gurmarin (Gur), a polypeptide isolated from the plant Gymnema sylvestre, is known to selectively suppress behavioral and gustatory neural responses to various sweet compounds without affecting responses to salty, sour and bitter substances in rodents (Imoto et al., 1991
; Miyasaka and Imoto, 1995; Ninomiya and Imoto, 1995; Ninomiya et al., 1997, 1998, 1999; Harada and Kasahara, 2000; Lemon et al., 2003; Murata et al., 2003). In mice, the sweet-suppressing effect of Gur differs among strains and taste nerves. Responses to sweet compounds in the chorda tympani (CT) nerve innervating the anterior tongue were inhibited to 
50% of control by Gur in C57BL/6 and C57BL/KsJ (abbreviated C57BL for either) but only slightly if at all in BALB/c (BALB) mice (Ninomiya and Imoto, 1995; Ninomiya et al., 1997). The inhibitory effect of Gur was not clearly evident in responses of the glossopharyngeal (IXth) nerve innervating the posterior tongue even in C57BL mice (Ninomiya et al., 1997). The effect of Gur is normally long-lasting (>2–3 h) but rapidly disappears after rinsing the tongue with either anti-gurmarin serum in rats (Imoto et al., 1991; Miyasaka and Imoto, 1995) or ß-cyclodextrin in C57BL mice (Ninomiya et al., 1998). This quick recovery from inhibition by Gur by rinsing the tongue with Gur-binding agents indicates that Gur may directly interact with taste receptors on the taste cell membrane in rodents.
Recently, the taste receptor T1R3 was identified as the gene product of a single locus, Sac (Tas1r3), on mouse chromosome 4 (Bachmanov et al., 2001; Kitagawa et al., 2001; Max et al., 2001; Montmayeur et al., 2001; Sainz et al., 2001); Sac had been shown to influence behavioral and nerve responses to artificial sweeteners, such as saccharin, and to several sugars (Fuller, 1974; Lush 1989; Bachmanov et al., 1997; Li et al., 2001). Differences between taster (C57BL) and non-taster (BALB, various sublines of the 129 strain etc.) strains in behavioral and nerve responses to sweet compounds are thus believed to be caused by polymorphisms in the Tas1r3 gene (e.g. six amino acid changes, including I60T). The T1R3 protein is proposed to form a heterodimer with T1R2 protein; this combination responds to many sweet compounds (Nelson et al., 2001, 2002). Knockout mice lacking T1R3 showed no preference for artificial sweeteners and had largely diminished behavioral and nerve responses to sugars (Damak et al., 2003; Zhao et al., 2003). This large contribution of T1R3 for reception of sweet compounds raises the possibility that strain differences in sensitivity to Gur, as mentioned above, may also be due to polymorphisms of Tas1r3.
To investigate this possibility, our previous study (Shigemura et al., 2005) examined the effect of Gur on CT responses to sucrose in the dpa-congenic strain having the same genetic background to BALB mice except the gene segment containing the dpa locus derived from C57BL mice. Similar to the Sac/Tas1r3 locus, the dpa locus has been proposed to locate on the mouse chromosome 4 and influence behavioral and nerve responses to sweet compounds including a sweet tasting amino acid, D-phenylalanine, and sugars (Ninomiya et al., 1991; Bachmanov et al., 1997). We found clear Gur inhibition of sucrose responses of the congenic strain, suggesting the possibility that Gur-sensitivity in mice may be independent of the Tas1r3 allele. Since, in a previous study (Shigemura et al., 2005), we examined only one single particular site (I60T, which was digested by a restriction enzyme, DraIII) (Montmayeur et al., 2001), and no other sites (e.g. five other amino acid changes) of the Tas1r3 allele in the congenic strain, further studies are needed to determine whether mouse strain differences in Gur-sensitivity may relate to polymorphisms of Tas1r3 or not.
In the present study, therefore, we examined the effect of Gur on CT responses to sweet compounds in non-taster 129 mice, a strain used previously for various genetic studies of Tas1r3 and shown to possess the non-taster Tas1r3 allele (e.g. six amino acid changes: Kitagawa et al., 2001; Nelson et al., 2001; Max et al., 2001; Inoue et al., 2004; Reed et al., 2004). Our results indicated that this non-taster strain clearly showed inhibition by Gur of CT responses to various sweet compounds similar to that observed in C57BL mice having the Tas1r3 taster genotype. This suggests that mouse strain differences in sensitivity to the sweet-suppressing effect of Gur may not be associated with polymorphisms in Tas1r3.
|
Materials and methods |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Subjects
All experimental procedures were approved by the committee for Laboratory Animal Care and Use at Kyushu University, Japan. Subjects were adult male and female 129X1/SvJ (formerly 129/SvJ) mice at 8–25 weeks of age (18–30 g body wt, n = 12), originally purchased from The Jackson Laboratory (Bar Harbor, ME). This strain possesses the Tas1r3 non-taster genotype (Kitagawa et al., 2001; Nelson et al., 2001, 2002). Animals were housed in plastic cages under a 12 h light/12 h dark cycle at 20–22°C and 50–55% relative humidity. Two or three mice were housed together in a cage and received food pellets ad libitum (MF; Oriental Yeast, Tokyo, Japan) and tap water.
Recordings of responses from the CT nerve
The procedures of dissection and recording of responses of the CT nerve were the same as those previously reported (Yasumatsu et al., 2003). Briefly, under pentobarbital anesthesia (50–60 mg/kg i.p.; Somnopentyl; Schering-Plough Co., Kenilworth, NJ), the trachea of each animal was cannulated, and the mouse was then fixed in the supine position with a head holder to allow dissection of the CT nerve. The hypoglossal nerve was transected bilaterally to prevent tongue movements. The right CT nerve was exposed at its exit from the lingual nerve by removal of medial pterygoid muscle. The CT nerve was then dissected free from surrounding tissues and cut at the point of its entry to the bulla. For whole-nerve recording, the entire nerve was placed on a silver wire electrode. An indifferent electrode was placed in nearby tissue. Neural responses resulting from chemical stimulations of the tongue were fed into an amplifier (Iyodenshikogaku K-1, Nagoya, Japan), monitored on an oscilloscope and audiomonitor. Whole nerve responses were integrated with a time constant of 1.0 s and recorded a computer for later analysis using PowerLab system (PowerLab/sp4; ADInstruments, Australia).
Chemical stimulations to the tongue
The anterior half of the tongue was enclosed in a flow chamber made of silicone rubber (Ninomiya and Funakoshi, 1981). Solutions were delivered into the chamber by gravity flow, and flowed over the tongue for a controlled period. Solutions used as chemical stimuli were: 0.01–1.0 M sucrose (Suc), 0.5 M maltose, 0.5 M fructose (Fru), 0.5 M glucose (Glu), 0.02 M saccharin Na (Sac), 0.3 M D-alanine (D-Ala), 1.0 M glycine (Gly), 0.1 M NH4Cl, 0.1 M NaCl, 0.01 M HCl and 0.02 M quinine–HCl (quinine) (Wako Pure Chemicals Industries, Osaka, Japan). These chemicals were dissolved in distilled water and used at 24°C. During chemical stimulation of the tongue, test solution flowed for 30 s at the same flow rate as the distilled water used for rinsing the tongue (0.1 ml/s). The tongue was rinsed with distilled water during the interval of 1 min between successive stimulations. To examine Gur inhibition of the CT responses, the tongue was treated with 30 µg/ml (7.1 µM) Gur dissolved in 5 mM phosphate buffer (pH 6.8; made with Na2HPO4.12H2O and NaH2PO4.2H2O) for 10 min in the same manner as that described by Ninomiya and Imoto (1995). Taste stimuli were applied first without Gur treatment, then the tongue was treated with Gur, and then the same taste stimuli were applied again. The concentration of Gur (30 µg/ml) was chosen because in C57BL mice the suppressive effect of Gur on sucrose responses in the CT nerve had been shown to be nearly maximal at this dose (Ninomiya and Imoto, 1995; Ninomiya et al., 1997, 1998). Application of the solvent without Gur by itself has no effect on the neural measurement. The stability of the preparation was monitored by periodic application of 0.1 M NH4Cl. A recording was considered to be stable when magnitudes of NH4Cl response at the beginning and end of each stimulation series deviated by no more than 15%. Only responses from stable recordings were used in the data analysis.
Data analysis
In the analysis of whole nerve responses, the magnitude of the integrated responses from 5 to 20 s after stimulus onset were measured and averaged. Relative response magnitude (averaged) for each test stimulus was calculated when the response magnitude to 0.1 M NH4Cl was taken as unity (1.0), and this value was used for statistical analysis. To evaluate the effect of Gur on taste responses statistically, data were analyzed using a two-way repeated-measures analysis of variance (ANOVA) and Student's t-test. All calculations were performed using the statistical software package StatView (Abacus Concepts, Inc., Berkeley, CA).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Figure 1 shows sample recordings of the integrated responses of the CT nerve of a 129 mouse to seven taste stimuli before and after lingual application with Gur. The Gur treatment selectively suppressed responses to sweet compounds to
50% of control, whereas no such suppression by Gur was observed in responses to 0.1 M NaCl, 0.01 M HCl or 0.02 M quinine. Relative magnitudes of responses to 0.1 M NaCl, 0.01 M HCl and 0.02 M quinine after Gur in 129 mice were 0.75, 1.20 and 0.70, respectively, which were not significantly different from those before (t-test, P > 0.05, Figure 3), as previously reported in C57BL and BALB mice (Ninomiya and Imoto, 1995; Ninomiya et al., 1997). As seen in Figure 2, responses to Suc after the Gur treatment was significantly different from that before [ANOVA, F(1,40) = 8.85, P < 0.05]. Student's t-tests indicate significant suppression of sucrose responses at 0.1, 0.3, 0.5 and 1.0 M after Gur (P < 0.05). Responses to Suc at these concentrations reduced to 50% of control [i.e. at 0.5 M: 0.69 ± 0.05 (mean ± SD) before and 0.33 ± 0.04 after Gur, n = 5], similar to that previously observed in C57BL mice (i.e. at 0.5 M: 1.01 ± 0.05 before and 0.52 ± 0.18 after Gur, n = 12; Ninomiya and Imoto, 1995). Responses to all sweet compounds tested, such as 0.5 M Glu, 0.5 M Mal, 0.5 M Fru, 1.0 M Gly, 0.3 M D-Ala and 0.02 M Sac, were also suppressed to 50% of control by Gur (t-test, P < 0.05, Figure 3). These results were consistent with those previously obtained from the Tas1r3 taster, C57BL strain (Ninomiya and Imoto, 1995). This suggests that the Tas1r3 non-taster strain, 129 mice, unlike another non-taster strain, BALB mice, clearly show Gur-sensitivity in their CT responses to sweet compounds. Thus, Gur-sensitivity in mice appears not to be associated with the Tas1r3 genotype.
|
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
It was known that mouse strains possessing different alleles of Tas1r3 have different Gur sensitivities (Gur-sensitive/taster C57BL versus Gur-insensitive/non-taster BALB) (Ninomiya and Imoto, 1995
; Kitagawa et al., 2001; Montmayeur et al., 2001; Reed et al., 2004). Our previous study have shown that congenic mice have at least one same amino acid change (I60T) of the Tas1r3 allele as BALB mice, but differ from BALB in Gur sensitivity, suggesting the possibility that Gur sensitivity may not be determined by the Tas1r3 locus (Shigemura et al., 2005). To further investigate this possibility, the present study examined the Gur sensitivity of another non-taster strain (129) possessing non-taster Tas1r3 allele (e.g. six amino acid changes, including I60T). Our results indicated that Gur (30 µg/ml) suppressed CT responses to sweet compounds in non-taster 129 mice to a similar extent (50% of control for 0.02 M Sac and 0.1–1.0 M Suc responses) to that found in taster C57BL mice. Since T1R3-knockout mice in the C57BL genetic backgrounds show CT responses to 0.02 M Sac and 0.3 M Suc that are only 12 and 20% of those of wild type C57BL mice (Damak et al., 2003), respectively, most of the Gur-sensitive and Gur-insensitive components of the sweet responses in mice are likely to occur through activation of T1R3-containing receptor(s). Taking this into consideration, polymorphic variations in the amino acid sequences of the T1R3 protein (e.g. six amino acid changes, including I60T) in mice may not influence the receptor's interaction with Gur greatly, even though this variation produces clear segregation between taster C57BL and non-taster 129 strains in their sensitivities to sweet compounds (Inoue et al., 2001, 2004; Nelson et al., 2001).
Although the 129 inbred strain is the most widely used strain in gene targeting experiments, numerous substrains exist with differences in their genomic sequences [e.g. simple sequence length polymorphisms (SSLPs)] (Threadgill et al., 1997). In the present study, we used the same 129X1/SvJ strain (formerly 129/SvJ) as used in previous studies (Nelson et al., 2001; Zhao et al., 2003), which differs in 52–54 out of 212 SLPs (25%) from the other 129 substrains (Threadgill et al., 1997), such as 129P3/J (formerly 129/J) and 129S1/SvImJ or 129T2/SvEmsJ (formerly 129/Sv) used in other taste studies (formerly 129/J: Bachmanov et al., 1997; Li et al., 2001; Inoue et al., 2004; Reed et al., 2004; formerly 129/Sv: Wong et al., 1996; Montmayeur et al., 2001; Damak et al., 2003; He et al., 2004). Our preliminary data indicates that amiloride-sensitivity of NaCl responses differ among 129 substrains. In 129X1/SvJ strain, amiloride suppressed CT responses to 0.1–1.0 M NaCl to 50% of control similar to C57BL mice (K. Yasumatsu et al., unpublished observation), whereas no such inhibition was evident in 129P3/J mice (Ninomiya et al., 1996; Gannon and Contreras, 1995). Therefore, it is also possible that differences in genetic background may cause differences in the Gur-sensitivity among 129 substrains, although no comparison has been made yet. With regards to CT responses to sweet compounds, 129X1/SvJ mice used in the present study showed similar magnitudes of responses to 1.0 M Suc (1.1), 0.02 M Sac (0.6) and 1.0 M Gly (0.8) as those shown by 129P3/J mice (Inoue et al., 2001). Only responses to 0.5 M Mal appeared slightly larger in 129X1/SvJ (0.25) than in 129P3/J mice (0.1; Inoue et al., 2001). Responses to all of these sweet compounds in 129P3/J and 129X1/SvJ mice were smaller than those in C57BL mice (Inoue et al., 2001; Yasumatsu et al., unpublished observation). This similar responses to sweet compounds between two 129 substrains may be due to their same Tas1r3 non-taster genotype (Bachmanov et al., 2001; Kitagawa et al., 2001; Nelson et al., 2001; Max et al., 2001; Montmayeur et al., 2001).
If Gur inhibits CT responses to sweet compounds through its interaction with the T1R2/T1R3 heterodimer, then it is unclear why Gur inhibits CT responses of one Tas1r3 non-taster (129, this study), but not of another non-taster strain (BALB) (Ninomiya and Imoto, 1995). Furthermore, if T1R2/T1R3 is the site of Gur's action and given that taste buds in BALB, 129 and C57BL mice in the anterior tongue innervated by CT nerve and in the posterior tongue innervated by the IXth nerve express both T1R2 and T1R3 (Kitagawa et al., 2001; Max et al., 2001; Nelson et al., 2001; Kim et al., 2003; Shigemura et al., unpublished observation), it is unclear why Gur inhibits nerve responses to sweet compounds of the CT but not of the IXth nerve (Ninomiya et al., 1997).
It may be that Gur-insensitive components of sweet responses in the CT and IXth nerves in 129 and C57BL mice may be mediated by sweet taste receptors other than T1R3-containing T1R2/T1R3 heterodimers (e.g. T1R2 monomers/homodimers or other hypothetical sweet taste receptors). This may be supported by the fact that T1R3-knockout mice exhibited no significant reduction in Gur-insensitive IXth nerve responses to sucrose, except at a concentration of 1.0 M, and showed diminished, but not abolished, responses to sugars in the Gur-sensitive CT nerve, as mentioned above (Damak et al., 2003); however, CT responses to various sweet compounds were almost abolished in double knockout mice lacking both T1R2 and T1R3 proteins (Zhao et al., 2003).
Gur insensitivity in BALB mice may not relate to the T1R2/T1R3 receptor itself or its components. dpa-congenic mice having non-taster BALB genetic backgrounds (including at least one particular site of Tas1r2 and Tas1r3) except for the gene segment (including the dpa locus) derived from the donor, taster C57BL strain, showed Gur inhibition of CT responses to sweet compounds (Shigemura et al., 2005). This observation suggests no major contribution of the Tas1r3 or Tas1r2 genotype to the Gur sensitivity in mice. If functional receptors for sweet compounds are limited within possible combinations of monomers and dimers of T1R2 and T1R3, it seems likely that the gene segment including the dpa locus in congenic mice may influence the factor involved in downstream signal transduction for the Gur-sensitive response component occurring through the T1R2/T1R3 receptor. To clarify these possibilities, however, future extensive studies are needed.
In summary, the present study examined the effect of Gur in 129 mice carrying Tas1r3 non-taster genotype. If Gur's site of action is the T1R2/T1R3 sweet receptor, then our results indicate that polymorphic variation in the amino acid sequence of the T1R3 protein does not greatly influence this interaction.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
We thank Dr R.F. Margolskee for his valuable comments and suggestions on the manuscripts and Dr T. Imoto for helping us to purify Gur from the plant Gymnema sylvestre. This work was supported by Grant-in-Aids 15209061(Y.N.) for Scientific Research from Japan Society for the Promotion of Science.
|
References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Bachmanov, A.A., Reed, D.R., Ninomiya, Y., Inoue, M., Tordoff, M.G., Price, R.A. and Beauchamp, G.K. (1997) Sucrose consumption in mice: major influence of two genetic loci affecting peripheral sensory responses. Mamm. Genome, 8, 545–548.[CrossRef][ISI][Medline]
Bachmanov, A.A., Li, X., Reed, D.R., Ohmen, J.D., Li, S., Chen, Z., Tordoff, M.G., de Jong, P.J., Wu, C., West, D.B., Chatterjee, A., Ross, D.A. and Beauchamp, G.K. (2001) Positional cloning of the mouse saccharin preference (Sac) locus. Chem. Senses, 26, 925–933.
Damak, S., Rong, M., Yasumatsu, K., Kokrashvili, Z., Varadarajan, V., Zou, S., Jiang, P., Ninomiya, Y. and Margolskee, R.F. (2003) Detection of sweet and umami taste in the absence of taste receptor T1R3. Science, 301, 850–853.
Fuller, J.L. (1974) Single-locus control of saccharin preference in mice. J. Hered., 65, 33–36.
Gannon, K.S. and Contreaus, R.J. (1995) Sodium-intake linked to amiloride-sensitive gustatory transduction in C57BL/6J and 129/J mice. Physiol. Behav., 57, 231–239.[CrossRef][Medline]
Harada, S. and Kasahara, Y. (2000) Inhibitory effect of gurmarin on palatal taste responses to amino acids in the rat. Am. J. Physiol. Regul. Integr. Comp. Physiol., 278, R1513–R1517.
He, W., Yasumatsu, K., Varadarajan, V., Yamada, A., Lem, J., Ninomiya, Y., Margolskee, R.F. and Damak, S. (2004) Umami taste responses are mediated by 
-transducin and -gustducin. J. Neurosci., 24, 7674–7680.
Imoto, T., Miyasaka, A., Ishima, R. and Akasaka, K. (1991) A novel peptide isolated from the leaves of Gymnema sylvestre. I. Characterization and its suppressive effect on the neural responses to sweet taste stimuli in the rat. Comp. Biochem. Physiol. A, 100, 309–314.[CrossRef][Medline]
Inoue, M., McCaughey, S.A., Bachmanov, A.A. and Beauchamp, G.K. (2001) Whole nerve chorda tympani responses to sweeteners in C57BL/6ByJ and 129P3/J mice. Chem. Senses, 26, 915–923.
Inoue, M., Reed, D.R., Li, X., Tordoff, M.G., Beauchamp, G.K. and Bachmanov, A.A. (2004) Allelic variation of the Tas1r3 taste receptor gene selectively affects behavioral and neural taste responses to sweeteners in the F2 hybrids between C57BL/6ByJ and 129P3/J mice. J. Neurosci., 24, 2296–2303.
Kim, M., Kusakabe, Y., Miura, H., Shindo, Y., Ninomiya,Y. and Hino, A. (2003) Regional expression patterns of taste receptors and gustducin in the mouse tongue. Biochem. Biophys. Res. Commun., 312, 500–506.[CrossRef][ISI][Medline]
Kitagawa, M., Kusakabe, Y., Miura, H., Ninomiya, Y. and Hino, A. (2001) Molecular genetic identification of a candidate receptor gene for sweet taste. Biochem. Biophys. Res. Commun., 283, 236–242.[CrossRef][ISI][Medline]
Lemon, C.H., Imoto, T. and Smith, D.V. (2003) Differential gurmarin suppression of sweet taste responses in rat solitary nucleus neurons. J. Neurophysiol., 90, 911–923.
Li, X., Inoue, M., Reed, D.R., Huque, T., Puchalski, R.B., Tordoff, M.G., Ninomiya, Y., Beauchamp, G.K. and Bachmanov, A.A. (2001) High-resolution genetic mapping of the saccharin preference locus (Sac) and the putative sweet taste receptor (T1R1) gene (Gpr70) to mouse distal chromosome 4. Mamm. Genome, 12, 13–16.[CrossRef][ISI][Medline]
Lush, I.E. (1989) The genetics of tasting in mice. VI. saccharin, acesulfame, dulcin and sucrose. Genet. Res., 53, 95–99.[ISI][Medline]
Max, M., Shanker, Y.G., Huang, L., Rong, M., Liu, Z., Campagne, F., Weinstein, H., Damak, S. and Margolskee, R.F. (2001) Tas1R3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat. Genet., 28, 58–63.[CrossRef][ISI][Medline]
Miyasaka, A. and Imoto, T. (1995) Electrophysiological characterization of the inhibitory effect of a novel peptide gurmarin on the sweet taste response in rats. Brain Res., 676, 63–68.[CrossRef][ISI][Medline]
Montmayeur, J.P., Liberles, S.D., Matsunami, H. and Buck, L.B. (2001) A candidate taste receptor gene near a sweet taste locus. Nat. Neurosci., 4, 492–498.[ISI][Medline]
Murata, Y., Nakashima, K., Yamada, A., Shigemura, N., Sasamoto, K. and Ninomiya, Y. (2003) Gurmarin suppression of licking responses to sweetener–quinine mixtures in C57BL mice. Chem. Senses, 28, 237–243.
Nelson, G., Hoon, M.A., Chandrashekar, J., Zhang, Y., Ryba, N.J.P. and Zuker, C.S. (2001) Mammalian sweet taste receptors. Cell 106, 381–390.[CrossRef][ISI][Medline]
Nelson, G., Chandrashekar, J., Hoon, M.A., Feng, L., Zhao, G., Ryba, N.J.P. and Zuker, C.S. (2002) An amino-acid taste receptor. Nature 416, 199–202.[CrossRef][Medline]
Ninomiya, Y. and Funakoshi, M. (1981) Responses of rat chorda tympani fibers to electrical stimulation of the tongue. Jpn. J. Physiol., 31, 559–570.[ISI][Medline]
Ninomiya, Y. and Imoto, T. (1995) Gurmarin inhibition of sweet taste responses in mice. Am. J. Physiol., 268, R1019–R1025.
Ninomiya, Y., Sako, N., Katsukawa, H. and Funakoshi, M. (1991) Taste receptor mechanisms influenced by a gene on chromosome 4 in mice. In Wysocki, C.J. and Kare, M.R. (eds), Chemical Senses, Vol. 3. Genetics of Perception and Communication. Marcel Dekker, New York, pp. 267–278.
Ninomiya, Y., Fukami, Y., Yamazaki, K. and Beauchamp, G.K. (1996) Amiloride inhibition of chorda tympani responses to NaCl and its temperature dependency in mice. Brain Res., 708, 153–158.[CrossRef][ISI][Medline]
Ninomiya, Y., Inoue, M., Imoto, T. and Nakashima, K. (1997) Lack of gurmarin sensitivity of sweet taste receptors innervated by the glossopharyngeal nerve in C57BL mice. Am. J. Physiol., 272, R1002–R1006.
Ninomiya, Y., Inoue, M. and Imoto, T. (1998) Reduction of the suppressive effects of gurmarin on sweet taste responses by addition of beta-cyclodextrin. Chem. Senses, 23, 303–307.[Abstract]
Ninomiya, Y., Imoto, T. and Sugimura, T. (1999) Sweet taste responses of mouse chorda tympani neurons: existence of gurmarin-sensitive and -insensitive receptor components. J. Neurophysiol., 81, 3087–3091.
Reed, D.R., Li, S., Li, X., Huang, L., Tordoff, M.G., Starling-Roney, R., Taniguchi, K., West, D.B., Ohmen, J.D., Beauchamp, G.K. and Bachmanov, A.A. (2004) Polymorphisms in the taste receptor gene (Tas1r3) region are associated with saccharin preference in 30 mouse strains. J. Neurosci., 24, 938–946.
Sainz, E., Korley, J.N., Battey, J.F. and Sullivan, S.L. (2001) Identification of a novel member of the T1R family of putative taste receptors. J. Neurochem., 77, 896–903.[CrossRef][ISI][Medline]
Shigemura, N., Yasumatsu, K., Yoshida, R., Sako, N., Katsukawa, H., Nakashima, K., Imoto, T. and Ninomiya, Y. (2005) The role of the dpa locus in mice. Chem. Senses, 30, i84–i85.
Threadgill, D.W., Yee, D., Martin, A., Nadeau, J.H. and Magnuson, T. (1997) Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain. Mamm. Genome, 8, 390–393.[CrossRef][ISI][Medline]
Wong, G.T., Gannon, K.S. and Margolskee, R.F. (1996) Transduction of bitter and sweet taste by gustducin. Nature, 381, 796–800.[CrossRef][Medline]
Yasumatsu, K., Katsukawa, H., Sasamoto, K. and Ninomiya, Y. (2003) Recovery of amiloride-sensitive neural coding during regeneration of the gustatory nerve: behavioral/neural correlation of salt discrimination. J. Neurosci., 23, 4362–4368.
Zhao, C.Q., Zhang, Y., Hoon, M.A., Chandrashekar, J., Erlenbach, I., Ryba, N.J.P. and Zuker, C.S. (2003) The receptor for mammalian sweet and umami taste. Cell, 115, 255–266.[CrossRef][ISI][Medline]
Accepted May 3, 2005
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||