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.
Iwata
K
K
Research and Development Laboratories, Maruho Co., Ltd., Osaka, Japan.
Murakami
N
N
Takase
H
H
Saito
T
T
Naruse
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001639:Bicarbonates / Q000378:metabolism*; D051546:Cyclooxygenase 2; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000633:toxicity*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009578:Nitrobenzenes / Q000633:toxicity*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001639:Bicarbonates; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin