Nonsalicylate nonsteroidal antiinflammatory drugs augment prestimulated acid secretion in rabbit parietal cells. Investigation of the mechanisms of action.
The effects of nonsalicylate nonsteroidal antiinflammatory drugs on acid secretion were studied in isolated rabbit parietal cells. Indomethacin, naproxen, and carprofen (10(-6)-10(-4) mol/L) potentiated histamine-, forskolin-, 3-isobutyl-1-methylxanthine-, and dibutyryl cyclic adenosine monophosphate-stimulated acid secretion without affecting basal acid secretion. This augmentation of secretagogue-stimulated acid secretion was dependent on extracellular calcium because potentiation was abolished by calcium depletion of the medium or in the presence of the calcium antagonist lanthanum chloride. Potentiation was independent of the H2 and muscarinic receptors and did not appear to involve guanine nucleotide regulatory proteins. Proton pump activity was unaffected by indomethacin. Furthermore, nonsteroidal antiinflammatory drugs increased calcium efflux through the plasma membrane, as measured by calcium 45, and decreased endogenous prostaglandin E2 content. Exogenous dimethyl prostaglandin E2 inhibited the potentiating effect of these drugs on histamine-stimulated but apparently not on dibutyryl cyclic adenosine monophosphate-stimulated acid secretion. The data indicate that nonsalicylate nonsteroidal antiinflammatory drugs interacted at a postreceptor site between adenylate cyclase and the proton pump. The potentiating effects of these drugs were regulated by calcium and possibly modulated by prostanoids.
Levine
R A
RA
Department of Medicine, State University of New York Health Science Center, Syracuse.
Nandi
J
J
King
R L
RL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D009288:Naproxen / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D009288:Naproxen; C007005:carprofen; D002118:Calcium; D007213:Indomethacin