Pineal gland G-protein coupled P2Y(1) receptors potentiate noradrenaline-induced N'-acetylserotonin production, a long term response which occurs after 5 h incubation. In the current study we show that a short-term effect of stimulation of P2Y(1) receptors is the increase in extracellular acidification rate (ECAR), which is mediated by an increase in intracellular calcium concentration ([Ca(2+)](i)). The pD(2) values for ATP (3.06 +/- 0.12)-induced ECAR increase was significantly smaller (p < 0.01) than that for ADP (3.64 +/- 0.18), 2MeSATP (3.56 +/- 0.02) and 2MeSADP (3.65 +/- 0.13). The selective P2Y(1) receptor antagonists A3'P-5'P and A3'P-5'PS inhibited the increase in ECAR-induced by ADP. Clamping [Ca(2+)](i) with BAPTA (30 and 50 micromol/l) led to inhibition of ADP-induced increase in ECAR. Agonist and antagonist data indicate P2Y(1) activation leads to a [Ca(2+)](i)-dependent acidification of the extracellular medium.