Umami taste in mice uses multiple receptors and transduction pathways

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. 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), 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.