Molecular Mechanism of Enhancement in Basic Tastes by Kokumi Substances: A Potent Calcium-Sensing Receptor (CaSR) Agonist, γ-Glutamyl-Valinyl-Glycine, Amplifies Sweet-Induced ATP Secretion Via Cell-to-Cell Communication in a Mouse Taste Bud

Previously, we reported that agonists for the calcium-sensing receptor CaSR enhance the intensity of salty, sweet, and umami tastes. Interestingly, CaSR agonists enhance specific basic tastes but do not elicit any taste themselves. In the present study, we characterized how CaSR agonists specifically affect sweet taste. We found that the CaSR agonist, γ-glutamyl-valinyl-glycine, enhanced ATP secretion from isolated mouse circumvallate taste buds triggered by an artificial sweetener, SC45647. This enhancement was abolished by atropine, implicating the involvement of muscarinic cholinergic mechanisms in the perception of kokumi substances. Moreover, nearly all CaSR-immunopositive taste cells co-expressed cholinergic markers, suggesting that CaSR-positive taste cells contain acetylcholine. These observations indicate that CaSR agonists enhance sweet-induced ATP release from sweet receptor cells via cholinergic cell-to-cell (paracrine) signaling within a taste bud.