Extracellular ATP prevents the release of stored Ca2+ by autonomic agonists in rat submandibular gland acini.
In dose-dependent fashion, extracellular ATP reduces the increase in cytosolic Ca2+ concentration ([Ca2+]o) due to mobilization of cellular Ca2+ stores by both epinephrine [half-maximal inhibitory concentration (IC50) = 35.7 +/- 12.9 microM; Hill coefficient (NH) = -2.0 +/- 0.7, n = 8] and by carbachol (IC50 = 27.0 +/- 7.0 microM, NH = -2.3 +/- 0.7, n = 9). Inhibition is due to ATP4- but does not result from any emptying or inaccessibility of Ca2+ stores, which are readily mobilized by thapsigargin in the presence of ATP4-. Reduction of Ca2+ 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) adenosine 5'-triphosphate (BZATP) is more potent than ATP in reducing [Ca2+]i due to mobilization of stored Ca2+ by either carbachol or epinephrine (IC50 for carbachol = 3.9 +/- 0.4 microM, NH = -3.2 +/- 0.5; IC50 for epinephrine = 3.8 +/- 0.2, NH = -2.6 +/- 0.7, n = 3) but GTP, UTP, ADP, and adenosine do not inhibit mobilization of stored Ca2+ by either carbachol or epinephrine. Neither ATP nor BZATP prevents the influx of extracellular Ca2+ stimulated by carbachol or epinephrine. These results suggest that ATP inhibits Ca2+ mobilization by autonomic neurotransmitters after occupation of P2Z purinoceptors.
Hurley
T W
TW
Department of Child Health, School of Medicine, University of Missouri-Columbia 65212.
Shoemaker
D D
DD
Ryan
M P
MP
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000345:Affinity Labels; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D007700:Kinetics; D051381:Rats; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013997:Time Factors
D000345:Affinity Labels; D013729:Terpenes; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D002118:Calcium; D004837:Epinephrine