Kazumi Iwata, Naofumi Murakami, Hiroshi Takase, Takako Saito and Tomohiro
Naruse
Research and Development Laboratories, Maruho Co., Ltd, 1-8-23 Oyodo
Naka, Kita-ku, Osaka 531, Japan
Abstract: 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.
Keywords: Indomethacin, NS-398, Duodenal bicarbonate