Comparative study of the effects of indomethacin and NS-398, a selective cyclooxygenase 2 inhibitor, on duodenal bicarbonate secretion induced by luminal acidification in rats

To clarify the mechanisms of duodenal ulcerogenic activity of non-steroidal anti-inflammatory drugs (NSAIDs), the effects of indomethacin (IND) on acid-stimulated duodenal bicarbonate secretion and histamine-induced duodenal ulcerogenic responses were studied in comparison with NS-398, a selective cyclooxygenase (COX)-2 inhibitor, in rats. IND (1 and 5 mg/kg, s.c.) significantly decreased duodenal bicarbonate secretion and potentiated duodenal lesion in a dose-dependent manner. On the other hand, NS-398 had no effect on these parameters. These findings suggest that duodenal ulcerogenicity of IND in the presence of histamine is mainly due to the inhibitory action on acid-stimulated bicarbonate secretion mediated by COX-1, but not by COX-2.