Umami taste in mice uses multiple receptors and transduction pathways

Abstract

Non-technical summary The distinctive umami taste elicited by L-glutamate and some other amino acids is thought to be initiated by G-protein-coupled receptors, such as heteromers of taste receptor type 1, members 1 and 3, and metabotropic glutamate receptors 1 and 4. We demonstrate the existence of multiple types of glutamate-sensitive gustatory nerve fibres and the contribution of multiple receptors and transduction pathways to umami taste. Such multiple systems for umami taste may differentially contribute to the behavioural preference for glutamate and discriminability of glutamate taste. AbstractThe 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. Ami, amiloride; CPPG, (RS)-α-cyclopropyl-4-phosphonophenylglycine; CT, chorda tympani; ENaC, epithelial sodium channel; GAD67, glutamate decarboxylase 67; GL, glossopharyngeal; GMP, guanosine monophosphate; HEK, human embryonic kidney; IMP, inosine monophosphate; IP 3 R3, inositol 1,4,5-trisphosphate receptor 3; KO, knockout; L-Ala, L-alanine; L-AP4, L-(+)-2-amino-4-phosphonobutyrate; L-Arg, L-arginine hydrochloride; L-Cys, L-cysteine; L-Lys, L-lysine hydrochloride; mGluR1(mGluR4), metabotropic glutamate receptor type 1 (type 4); MPG, monopotassium glutamate; MSG, monosodium glutamate; NMDA, N -methyl-D-aspartic acid; QHCl, quinine hydrochloride; Quis, quisqualic acid; Suc, sucrose; TRPM5, transient receptor potential cation channel subfamily M member 5; WT, wild-type.

Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion

“…It has been suggested that there are multiple receptors for amino acid sensing in the lingual epithelium (67). It is likely that a similar situation may exist in the gut.…”

“…Among the proposed lingual and/or intestinal epithelial amino acid receptors, T1R1-T1R3, mGluR4, mGluR1, and CaSR, only T1R1 contains all four critical residues required for IMP/GMP binding. Therefore, signal transduction in response to amino acids by other receptors cannot be enhanced by addition of these nucleotide monophosphate esters (67,70).…”

“…A salient feature of amino acid taste in animals and umami taste in humans is the synergistic enhancement of potency when Glu or other amino acids are combined with the monophosphate esters of inosine or guanosine nucleotides (64,65,67,69). The synergistic enhancement of umami taste by IMP or GMP is an exclusive property of T1R1-T1R3 (13,49,70,72).…”

The Physiology of Taste in Fish: Potential Implications for Feeding Stimulation and Gut Chemical Sensing

“…For instance, in mammals other candidates for the umami taste include taste-specific variants or isoforms of metabotropic glutamate receptors (mGluRs) such as mGluR1 and mGluR4, which are members of another class of GPCRs, binding L-glutamic acid (Yasumatsu et al, 2012).…”

Gustatory neural responses to umami stimuli in the parabrachial nucleus of C57BL/6J mice

“…Therefore, the response of neurons that seemingly are most strongly activated by MSG might merely reflect their sensitivity to other components than glutamate. It should be noted that a recent report showed the existence of S-best and MPG-best mouse CT fibers, each of which can be further divided into two subcategories that do or do not possess a synergistic response to an umami stimulus mixture (Yasumatsu et al 2011). Some mouse single fungiform taste cells are also known to respond best and specifically to MSG (Yoshida et al 2009).…”