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

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...

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Published in:The Journal of pharmacology and experimental therapeutics 2013-01, Vol.344 (1), p.189-195
Main Authors: Satoh, Hiroshi, Amagase, Kikuko, Ebara, Satomi, Akiba, Yasutada, Takeuchi, Koji
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cats
Celecoxib
Cimetidine - pharmacology
Cyclooxygenase 1 - metabolism
Cyclooxygenase 2 - metabolism
Cyclooxygenase 2 Inhibitors - pharmacology
Cyclooxygenase Inhibitors - pharmacology
Diet
Dinoprostone - metabolism
Duodenal Diseases - pathology
Duodenal Diseases - prevention & control
Duodenum - drug effects
Duodenum - metabolism
Female
Histamine H2 Antagonists - pharmacology
Immunohistochemistry
Intestinal Mucosa - pathology
Male
Pyrazoles - pharmacology
Sulfonamides - pharmacology
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Summary: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.
ISSN:0022-3565
1521-0103
DOI:10.1124/jpet.112.199182