Extracellular ATP prevents the release of stored Ca2+ by autonomic agonists in rat submandibular gland acini
Hurley, T.W.; Shoemaker, D.D.; Ryan, M.P.
American Journal of Physiology 265(6 Pt 1): C1472-C1478
1993
ISSN/ISBN: 0002-9513 PMID: 8279511 Document Number: 418023
In dose-dependent fashion, extracellular ATP reduces the increase in cytosolic Ca-2+concentration ((Ca-2+)-o) due to mobilization of cellular Ca-2+ stores by both epinephrine (half-maximal inhibitory concentration (IC-50) = 35.7 +- 12.9 AM; Hill coefficient (N-H) = -2.0 +- 0.7, n = 8) and by carbachol (IC-50 = 27.0 +- 7.0 mu-M, N-H = -2.3 +- 0.7, n = 9). Inhibition is due to ATP-4- but does not result from any emptying or inaccessibility of Ca-2+ stores, which are readily mobilized by thapsigargin in the presence of ATP-4-. Reduction of Ca-2+mobilization is rapid but is not due to direct interference by ATP with the interaction of carbachol or epinephrine with their respective cell surface receptors. A benzoyl derivative of ATP, 3'-O-(4-benzoyl) adensoine 5'-triphosphate (BZATP) is more potent than ATP in reducing (Ca-2+)-i due to mobilization of stored Ca-2+ by either carbachol or epinephrine (IC-50 for carbachol = 3.9 +- 0.4 mu-M, N-H = -3.2 +- 0.5; IC-50 for epinephrine = 3.8 +- 0.2, N-H = -2.6 +- 0.7, n = 3) but GTP, UTP, ADP, and adenosine do not inhibit mobilization of stored Ca-2+ by either carbachol or epinephrine. Neither ATP nor BZATP prevents the influx of extracellular Ca-2+ stimulated by carbachol or epinephrine. These results suggest that ATP inhibits Ca-2+ mobilization by autonomic neurotransmitters after occupation Of P-2Z purinoceptors.