Human genetic polymorphisms in T1R1 and T1R3 taste receptor subunits affect their function.

Umami is the typical taste induced by monosodium glutamate (MSG), which is thought to be detected by the heterodimeric G protein-coupled receptor, T1R1 and T1R3. Previously, we showed that MSG detection thresholds differ substantially between individuals and we further showed that nontaster and hypotaster subjects are associated with nonsynonymous single polymorphisms occurring in the T1R1 and T1R3 genes. Here, we show using functional expression that both amino acid substitutions (A110V and R507Q) in the N-terminal ligand-binding domain of T1R1 and the 2 other ones (F749S and R757C), located in the transmembrane domain of T1R3, severely impair in vitro T1R1/T1R3 response to MSG. A molecular model of the ligand-binding region of T1R1/T1R3 provides a mechanistic explanation supporting functional expression data. The data presented here support causal relations between the genotype and previous in vivo psychophysical studies in human evaluating sensitivity to MSG.

Nonsynonymous single nucleotide polymorphisms in human tas1r1, tas1r3, and mGluR1 and individual taste sensitivity to glutamate.

Several studies indicate an essential role of the heterodimer Tas1R1-Tas1R3 for monosodium l-glutamate (MSG) detection, although others suggest alternative receptors. Human subjects show different taste sensitivities to MSG, and some are unable to detect the presence of glutamate. Our objective was to study possible relations between phenotype (sensitivity to glutamate) and genotype (polymorphisms in candidate glutamate taste receptors tas1r1, tas1r3, mGluR4, and mGluR1) at the individual level. The sensitivity was measured with a battery of tests to distinguish the effect of sodium ions from the effect of glutamate ions in MSG. A total of 142 genetically unrelated white French subjects were categorized into 27 nontasters (specific ageusia), 21 hypotasters, and 94 tasters. Reverse transcriptase polymerase chain reaction and immunohistochemistry showed expression of tas1r1, tas1r3, and alpha-gustducin in fungiform papillae in all 12 subjects tested, including subjects who presented specific ageusia for glutamate. Amplification and sequencing of cDNA and genomic DNA allowed the identification of 10 nonsynonymous single nucleotide polymorphisms (nsSNPs) in tas1r1 (n = 3), tas1r3 (n = 3), and mGluR1 (n = 4). In our sample of subjects, the frequencies of 2 nsSNPs, C329T in tas1r1 and C2269T in tas1r3, were significantly higher in nontasters than expected, whereas G1114A in tas1r1 was more frequent in tasters. These nsSNPs along with minor variants and other nsSNPs in mGluR1, including T2977C, account for only part of the interindividual variance, which indicates that other factors, possibly including additional receptors, contribute to glutamate sensitivity.

Tas1R1-Tas1R3 taste receptor variants in human fungiform papillae.

Monosodium glutamate as well as metabotropic and ionotropic glutamate receptor agonists have been reported to be perceived as umami by humans. In spite of the fact that Tas1R1-Tas1R3 has been shown to mediate most of the glutamate taste sensation in mice other candidate receptors have been put forward for which a clear role in detection is still lacking. This work was aimed at investigating the molecular determinants underlying umami taste detection in humans. First, we show evidence supporting expression of Tas1R1 and Tas1R3 but not mGluRs in the fungiform papillae of several individuals. Next, we report a number of naturally occurring L-glutamate taste receptor variants and their frequency in a population of Caucasian subjects. Detailed analysis of 9 non-synonymous single nucleotide polymorphisms from three L-glutamate taste GPCR candidates uncovers receptor specific clusters such that all substitutions in Tas1R1 are located in the extracellular N-terminal ligand-binding domain while in Tas1R3 they mostly affect residues in the seven transmembrane-spanning core domain responsible for the interaction with antagonists and allosteric modulators. In mGluR1, nsSNPs identified are clustered in the intracellular C-terminal tail, which is thought to play a role in signaling. Taken together, these results suggest that Tas1R1-Tas1R3 receptor variants found in human fungiform papillae might contribute to inter-individual differences of sensitivity to L-glutamate.

Taste deficits after middle ear surgery for otosclerosis: taste somatosensory interactions.

The aim of this study was to evaluate the postoperative consequences of chorda tympani reclining during middle ear surgery for otosclerosis. Electrogustometric taste thresholds were measured at 11 loci on the tongue and the soft palate in 14 patients before surgery, and 8 d, 1 month and (in some cases) 6 months after surgery. A significant increase in thresholds was observed on the ipsilateral side of the tongue after surgery. The extent of the deficit and the recovery time course depended on tongue locus. The tip of the tongue displayed a limited deficit, suggesting bilateral chorda tympani innervation. The edge of the tongue was less impaired than the dorsal or the lateral tip loci; it may be dually innervated by both chorda tympani and glossopharyngeal nerves in humans, as already shown in rats. Likewise for the fungiform papillae located just anterior to the circumvallate papillae. Somatosensory early complaints suggest a derepression of chorda tympani on lingual nerve signals. In a second stage, relief of complaints before electrogustometric threshold recovery suggested trigeminal compensation of the chorda tympani deficit. Relief of complaints seems to involve central integrative processes, whereas the evolution of electrogustometric threshold represents the actual recovery time course of chorda tympani peripheral sensitivity.

Taste deficits related to dental deafferentation: an electrogustometric study in humans.

Dental treatments, the prevalence of which increases with age, can cause orofacial somatosensory deficits. In order to examine whether they may also affect taste sensitivity, electrogustometric thresholds were measured at 9 loci on the tongue surface in 391 healthy non-smoking, non-medicated subjects. Results showed that the greater the number of deafferented teeth, the higher the thresholds. Irrespective of age, subjects with more than 7 deafferented teeth exhibited significantly higher thresholds than subjects with fewer than 7 deafferented teeth. Conversely, across age groups, no statistical difference was observed among subjects with no, or few, deafferented teeth. Hence, a taste deficit, which was not correlated to aging, was observed. An association was noticed between the location of taste deficits and the location of deafferented teeth. Higher thresholds at anterior sites, with no possible traumatic injury relationship, suggested that neurophysiological convergence between dental somatosensory and taste pathways - possibly in the nucleus tractus solitarius - could be responsible for these relative decreases of taste sensitivity when dental afferences were lacking. Among trigeminal contributions, lingual nerve and inferior alveolar nerve may synergize taste.

Sensory interactions through neural pathways.

The word "taste" includes olfaction and somatosensory information besides the proper sense of taste. Taste and somatosensory sensitivity are very close and overlapping in most central nervous system projection areas. The objective of the present paper is to review a series of experiments disclosing functional neurophysiological interactions between taste and somatosensory information at different levels.

Modulation of taste peripheral signal through interpapillar inhibition in hamsters.

Single taste buds from fungiform papillae were iontophoretically stimulated with chemicals filling glass microelectrodes while a single unit was recorded in the taste pore of a neighbor papilla. High signal-to-noise ratio responses were observed in the recorded papilla as antidromic action potentials. These responses were possibly modulated by the simultaneous stimulation of another adjacent papilla. A decrease in the frequency of firing and/or both decrementing spikes were observed during such dual papillae stimulations. These inhibitory effects were not modified by the section of the chordo-lingual nerve, suggesting the tongue is able to process the gustatory information thanks to interpapillar negative feedback, prior to transmitting the signal to the central nervous system. Branched chorda tympani fibers can account for responses observed for single papillae stimulations; inhibitions and decrementing spikes may suggest the contribution of another mechanism of interaction between two different single fibers.

Trigeminal modulation of gustatory neurons in the nucleus of the solitary tract.

Electrophysiological methods were used to investigate the effects of trigeminal nerve stimulation or transection on responses of single gustatory neurons in the nucleus of the solitary tract (NTS) to tastants (NaCl, sucrose, citric acid, monosodium glutamate) in pentobarbital-anesthetized rats. Unilateral transection of the lingual nerve, or the mandibular branch of the trigeminal nerve, resulted in significant reductions (by 21 and 29%, respectively; P<0.01) in tastant-evoked responses, with no further effect following bilateral transection. Electrical stimulation of the central cut end of the mandibular nerve directly excited nine of 14 gustatory NTS units. For these units, central mandibular stimulation facilitated the tastant-evoked responses in six, depressed responses in three, and had no effect in five. Facilitation of tastant-evoked responses peaked 4 min after mandibular stimulation and recovered within 8 min. Electrical stimulation of the peripheral cut end of the mandibular nerve significantly reduced tastant-evoked responses in nine other NTS units, with a maximal reduction at 4 min post-stimulation followed by recovery. Stimulation of the superior cervical sympathetic ganglion did not affect NTS tastant-evoked responses. These results suggest the presence of complex central modulation of NTS neurons by trigeminal afferents, as well as a peripheral depressant effect on gustatory processing possibly mediated via neuropeptide release from trigeminal nerve endings in the tongue.