EXTRACELLULAR ATP PREVENTS THE RELEASE OF STORED CA2-GLAND ACINI( BY AUTONOMIC AGONISTS IN RAT SUBMANDIBULAR)

In dose-dependent fashion, extracellular ATP reduces the increase in c ytosolic Ca2+ concentration ([Ca2+]o) due to mobilization of cellular Ca2+ stores by both epinephrine [half-maximal inhibitory concentration (IC50) = 35.7 +/- 12.9 muM; Hill coefficient (N(H)) = -2.0 +/- 0.7, n = 8] and by carbachol (IC50 = 27.0 +/- 7.0 muM, N(H) = -2.3 +/- 0.7, n = 9). Inhibition ig due to ATP4- but does not result from any emptyi ng or inaccessibility of Ca2+ stores, which are readily mobilized by t hapsigargin in the presence of ATP4-. Reduction of Ca2+ mobilization i s rapid but is not due to direct interference by ATP with the interact ion of carbachol or epinephrine with their respective cell surface rec eptors. A benzoyl derivative of ATP, 3'-O-(4-benzoyl) adensoine 5'-tri phosphate (BZATP) is more potent than ATP in redUCing [Ca2+]i due to m obilization of stored Ca2+ by either carbachol or epinephrine (IC50 fo r carbachol = 3.9 +/- 0.4 muM, N(H) = -3.2 +/- 0.5; IC50 for epinephri ne = 3.8 +/- 0.2, N(H) = -2.6 +/- 0.7, n = 3) but GTP, UTP, ADP, and a denosine do not inhibit mobilization of stored Ca2+ by either carbacho l or epinephrine. Neither ATP nor BZATP prevents the influx of extrace llular Ca2+ stimulated by carbachol or epinephrine. These results sugg est that ATP inhibits Ca2+ mobilization by autonomic neurotransmitters after occupation Of P2Z purinoceptors.