By using photometry and the patch clamp technique, we identified P 2 Y -like receptors in mouse taste receptor cells (TRCs) and found them to be coupled to Ca 2 + mobilization and ionic current modulation. Particularly, adenosine triphosphate (ATP) and the P 2 Y agonist 2-methylthio-ATP increased intracellular Ca 2 + by stimulating the phosphoinositide pathway, whereas β,γ-methylene-d-ATP, a P 2 X agonist, was ineffective. In a distinctive TRC subpopulation, ATP closed Ca 2 + channels. This regulation may underlie the negative feedback tuning neurotransmitter release. By mobilizing intracellular Ca 2 + , ATP activated Ca 2 + -dependent Cl - channels, the intracellular event that may universally occur upon taste stimulation triggering IP 3 formation and Ca 2 + release in the TRC cytoplasm.