Effect of nimesulide on gastric acid secretion in the mouse stomach in vitro.
Nimesulide, a selective inhibitor of cyclooxygenase-2, has been reported to cause less gastric damage, compared to other NSAIDs. We investigated the effect of nimesulide on basal gastric acid secretion, a contributing factor in NSAID-induced gastric damage, and histamine, pentagastrin, 5-methylfurmethide, isobutyl methylxanthine or high K(+) stimulated acid secretion in the isolated mouse stomach. The stomachs, removed from mice, were transferred into an organ bath and continuously perfused. Changes in pH following the addition of secretagogues were measured by a pH electrode system. The effects of nimesulide on basal and secretagogues-stimulated acid secretion were compared to those of indomethacin. Nimesulide (1 microM to 100 microM) produced a rightward concentration-dependent shift and reduction of maximum acid secretion of all the agonist-stimulated acid secretion curves. Indomethacin was only effective at the higher concentration of 100 microM. Compared to their effects singly, nimesulide (20 microM) and famotidine (0.15 microM) together caused a further shift without further reduction in maximum acid output of the histamine-stimulated curve, suggesting that nimesulide was not acting at the histamine H(2)-receptor. Nimesulide concentration-dependent reduction of stimulated acid secretion in the isolated mouse stomach was not by antagonism of the histamine H(2) receptor and is probably beyond the level of adenylate cyclase stimulation. A direct effect on the calcium channel is demonstrated.
Borrelli
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Department of Experimental Pharmacology, University of Naples Federico II, via D. Montesano 49, 80131 Naples, Italy. franborr@cds.unina.it
Tavares
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D015738:Famotidine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013270:Stomach / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D006635:Histamine H2 Antagonists; D013449:Sulfonamides; D015738:Famotidine; D006632:Histamine; C012655:nimesulide; D007213:Indomethacin