title: Aspirin potentiates prestimulated acid secretion and mobilizes intracellular calcium in rabbit parietal cells.
abstract: 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.
authors.affiliation: Department of Medicine, State University of New York Health Science Center, Syracuse 13210.
authors.forename: R A
authors.initials: RA
authors.lastname: Levine
authors.forename: J
authors.initials: J
authors.lastname: Nandi
authors.forename: R L
authors.initials: RL
authors.lastname: King
mesh_terms: 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
chemical_list: 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