Cyclooxygenase (COX)-1 and COX-2 both play an important role in the protection of the duodenal mucosa in cats.

Hiroshi Satoh, Kikuko Amagase, Satomi Ebara, Yasutada Akiba, Koji Takeuchi

Department of Pharmacology & Experimental Therapeutics, Division of Pathologial Science, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan. h_satoh@mb.kyoto-phu.ac.jp

The Journal of pharmacology and experimental therapeutics 2013 Jan

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Although nonsteroidal anti-inflammatory drugs often cause ulcers in the duodenum in humans, the role of cyclooxygenase (COX) isoforms in the pathogenesis of duodenal ulcers has not been fully elucidated. We examined in cats the 1) ulcerogenic effects of selective COX-1 (SC-560, ketorolac) and COX-2 (celecoxib, meloxicam) inhibitors on the gastrointestinal mucosa, 2) effect of feeding and cimetidine on the expression of COX isoforms and prostaglandin E(2) (PGE(2)) level in the duodenum, and 3) localization of COX isoforms in the duodenum. COX inhibitors were administered after the morning meal in cats once daily for 3 days. Gastrointestinal lesions were examined on day 4. Localization and expression of COX isoforms (by immunohistochemistry, Western blot) and PGE(2) level (by enzyme immunoassay) were examined. Results were as follows. First, selective COX-1 or COX-2 inhibitors alone produced marked ulcers in the duodenum but did not cause obvious lesions in the small intestine. Coadministration of SC-560 and celecoxib produced marked lesions in the small intestine. Second, feeding increased both the expression of COX isoforms and PGE(2) level in the duodenum, and the effects were markedly inhibited by pretreatment with cimetidine. Third, COX-1 was localized in goblet and Brunner's gland cells, Meissner's and Auerbach's plexus, smooth muscle cells, and arterioles; and COX-2 was observed in capillaries, venules, and basal granulated cells. The expression of COX isoforms in the duodenum is up-regulated by feeding, and inhibition of either COX-1 or COX-2 causes ulcers in the duodenum, suggesting that both isoforms play an important role in the protection of the duodenal mucosa.

Citation

Hiroshi Satoh, Kikuko Amagase, Satomi Ebara, Yasutada Akiba, Koji Takeuchi. Cyclooxygenase (COX)-1 and COX-2 both play an important role in the protection of the duodenal mucosa in cats. The Journal of pharmacology and experimental therapeutics. 2013 Jan;344(1):189-95