P2Y purinoceptors induce changes in intracellular calcium in acinar cells of rat lacrimal glands.

ABSTRACT

Adenosine 5'-triphosphate (ATP) is an extracellular signal that regulates various cellular functions. Cellular secretory activities are enhanced by ATP as well as by cholinergic and adrenergic stimuli. The present study aimed to determine which purinoceptors play a role in ATP-induced changes in the intracellular concentration of calcium ions ([Ca²âº](i)) and in the fine structure of acinar cells of rat lacrimal glands. ATP induced exocytotic structures, vacuolation and an increase in [Ca²âº](i) in acinar cells. The removal of extracellular Ca²âº or the use of Ca²âº channel blockers partially inhibited the ATP-induced [Ca²âº](i) increase. U73122 (an antagonist of PLC) and heparin (an antagonist of IP3 receptors) did not completely inhibit the ATP-induced [Ca²âº](i) increase. P1 purinoceptor agonists did not induce any changes in [Ca²âº](i), whereas suramin (an antagonist of P2 receptors) completely inhibited ATP-induced changes in [Ca²âº](i). A P2Y receptor agonist, 2-MeSATP, induced a strong increase in [Ca²âº](i), although UTP (a P2Y2,4,6 receptor agonist) had no effect, and reactive blue 2 (a P2Y receptor antagonist) resulted in partial inhibition. The potency order of ATP analogs (2-MeSATP > ATP >>> UTP) suggested that P2Y1 played a significant role in the cellular response to ATP. BzATP (a P2X7 receptor agonist) induced a small increase in [Ca²âº](i), but α,ß-meATP (a P2X1,3 receptor agonist) had no effect. RT-PCR indicated that P2X2,3,4,5,6,7 and P2Y1,2,4,12,14 are expressed in acinar cells. In conclusion, the response of acinar cells to ATP is mediated by P2Y (especially P2Y1) as well as by P2X purinoceptors.