Abstract
Recent studies indicate an expression of mitogen-inducible cyclooxygenase (COX-2) in gastric mucosa. Rebamipide, a mucoprotective agent enhances prostaglandin (PG) synthesis. The present study was designed to clarify the mechanism for rebamipide-induced mucosal protection. Male Sprague-Dawley rats were administered 5, 15, or 50 mg/kg/day rebamipide for 14 days. The expression of constitutive cyclooxygenase (COX-1) and COX-2 in gastric mucosa was determined using Western blot analysis. Another series of rats was used to examine 1) the levels of PGE2 in stomach with and without pretreatment with a COX-2 inhibitor; 2) the protective action of rebamipide against gastric damage caused by 0.6 N HCl; and 3) the effects of a COX-2 inhibitor on rebamipide-induced gastric mucosal protection. COX-2 expression was enhanced, whereas COX-1 expression did not change significantly in the gastric mucosa of rats after treatment with rebamipide. The gastric mucosal PGE2 was higher in the rebamipide groups than in the vehicle-treated group. Rebamipide also suppressed gastric damage induced by HCl in a dose-dependent manner. A COX-2 inhibitor blocked the rebamipide-induced increase in mucosal PGE2, and mucosal protection induced by rebamipide. The results indicate that rebamipide induces COX-2 expression, increases PGE2 levels, and enhances gastric mucosal defense in a COX-2-dependent manner. Thus, COX-2 has an important role in the effects of rebamipide on gastric mucosal protection.
Footnotes
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Send reprint requests to: Shingo Tsuji, M.D., Ph.D., Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan. E-mail: tsuji{at}medone.med.osaka-u.ac.jp
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↵1 This study was supported by grants in aid from the Ministry of Health and Welfare, the Ministry of Education, Science, Sports and Culture, and the Smoking Research Foundation.
- Abbreviations:
- PG
- prostaglandin
- COX
- cyclooxygenase
- CMC
- carboxymethylcellulose
- EGF
- epidermal growth factor
- EGF-R
- epidermal growth factor-receptor
- NF-κB
- nuclear factor-κB
- Received March 27, 2000.
- Accepted July 5, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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