Umami taste in mice uses multiple receptors and transduction pathways

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), andmetabotropic 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 fromwild-type mice andmice 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) andmonopotassium 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 suppressedMPG responses of M1-andM2-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.