Aspirin potentiates prestimulated acid secretion and mobilizes intracellular calcium in rabbit parietal cells.
The effects of aspirin on gastric acid secretion were studied in isolated rabbit parietal cells (PC). Aspirin (10(-5) M) potentiated histamine-, dibutyryl cyclic AMP (dbcAMP)-, forskolin- and 3-isobutyl-1-methylxanthine-stimulated acid secretion without affecting basal acid secretion. Augmentation of secretagogue-stimulated acid secretion by aspirin was dependent on calcium (Ca2+) since potentiation was blocked by removal of extracellular Ca2+ ([Ca2+]o) or addition of the calcium antagonist lanthanum chloride. Using the Ca2+ probe fura-2, aspirin (10(-6) - 2 X 10(-5) M) rapidly increased intracellular free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. The source of released Ca2+ was intracellular as demonstrated by depletion of intracellular Ca2+ and [Ca2+]o with EGTA washing. Aspirin did not affect several other signal transduction sites involved in stimulus-secretion coupling, including the H2 receptor, intracellular cyclic AMP (cAMP), inositol 1,4,5, triphosphate (IP3) and H+,K(+)-ATPase. Aspirin decreased PC prostaglandin E2 (PGE2) content by 98%. Exogenous dimethyl PGE2 (dmPGE2) inhibited both histamine-stimulated acid secretion and its enhancement by aspirin. In contrast, dmPGE2 abolished aspirin-induced potentiation of dbcAMP-stimulated acid secretion by augmenting the dbcAMP-stimulated response. These results indicate that aspirin acts at a site beyond the adenylate cyclase/cAMP system and before the proton pump, presumably by releasing Ca2+ from an IP3-independent intracellular storage pool and by inhibiting PGE2 generation.
Levine
R A
RA
Department of Medicine, State University of New York Health Science Center, Syracuse 13210.
Nandi
J
J
King
R L
RL
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase; D007295:Inositol Phosphates / Q000378:metabolism; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000502:physiology; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D015398:Signal Transduction
D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D012459:Salicylates; D000632:Aminopyrine; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D015232:Dinoprostone; D020156:Salicylic Acid; D001241:Aspirin; D002118:Calcium