2 DISTINCT ATP RECEPTORS ACTIVATE CALCIUM-ENTRY AND INTERNAL CALCIUM-RELEASE IN BOVINE CHROMAFFIN CELLS

ATP, an established neurotransmitter, causes elevation of cytosolic Ca 2+ and catecholamine secretion when applied to chromaffin cells in the intact adrenal gland. The ATP-induced rise in Ca2+ is due both to rel ease from internal stores and to entry across the plasma membrane. The latter source of Ca2+ causes secretion; the primary role of Ca2+ rele ased from internal stores remains undetermined. In this article, we ha ve studied the nucleotide specificity for activating the two types of Ca2+ increases. The agonist potency order for the increase in fluoresc ence from fura-2-loaded chromaffin cells due to release of Ca2+ from i nternal stores is ATP = UTP > ADP > 2-methy(thio-ATP, alpha,beta-methy lene ATP, identifying the receptor as a P-2U purinoceptor. The potency order for secretion is 2-methylthio-ATP > ATP > alpha,beta-methylene ATP, ADP, UTP, placing the receptor in the P-2Y subtype. Thus, two dis tinct receptors are responsible for Ca2+ release and secretion. Agonis ts were more effective in the absence of extracellular Mg2+, suggestin g that ATP uncomplexed with divalent cations binds preferentially to b oth receptors. The low response of both receptors to ADP distinguishes them from the ATP receptor on these cells that inhibits voltage-depen dent Ca2+ current and secretion.