Involvement of multiple taste receptors in the actions of Kokumi taste stimuli

Kokumi taste stimuli are ligands that activate the calcium-sensing receptor (CaSR). Kokumi stimuli elicit flavor persistence and richness, and also modulate basic tastes, such as enhance salt taste. Most γ-glutamyl peptides produce Kokumi taste as natural allosteric modulators of CaSR. We investigated the effects of γ-Glu-Cys-Gly (GSH) and γ-Glu-Val-Gly (γ-EVG) on salt taste using patch clamp technique and calcium signaling. Salt detection is mediated by at least two pathways. A Na+ selective pathway that utilizes the amiloride (Am)-sensitive epithelial Na+ channel (ENaC), and a cation non-selective pathway that is Am-insensitive. Patch-clamp studies using rat fungiform taste cells expressing ENaC provided direct evidence that GSH and γ-EVG do not alter ENaC activity. We further investigated if Kokumi taste substances can modulate salt response via the Am-insensitive pathway(s). We monitored temporal changes in [Ca2+] in HEK293T cells expressing the human vanilloid receptor 1 (hTRPV1), a non-selective cation channel, which has been suggested as a potential Am-insensitive salt taste mediator. GSH and γ-EVG induced concentration-dependent changes in [Ca2+] that were markedly attenuated in the presence of capsazepine, a specific TRPV1 antagonist. In cells expressing capsaicin-insensitive hTRPV1 mutants, the apparent affinity of hTRPV1 for GSH and γ-EVG was significantly reduced. These results suggest that multiple taste receptors may be potentially involved in the actions of Kokumi taste stimuli.