Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide, a mucoprotective agent

Recent studies indicate an expression of mitogen-inducible cyclooxygenase ( COX-2) in gastric mucosa. Rebamipide, a mucoprotective agent enhances prost aglandin (PG) synthesis. The present study was designed to clarify the mech anism for rebamipide-induced mucosal protection. Male Sprague-Dawley rats w ere administered 5, 15, or 50 mg/kg/day rebamipide for 14 days. The express ion 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 PGE(2) in stomach with and without pretreatment wi th a COX-2 inhibitor; 2) the protective action of rebamipide against gastri c damage caused by 0.6 N HCl; and 3) the effects of a COX-2 inhibitor on re bamipide-induced gastric mucosal protection. COX-2 expression was enhanced, whereas COX-1 expression did not change significantly in the gastric mucos a of rats after treatment with rebamipide. The gastric mucosal PGE(2) was h igher in the rebamipide groups than in the vehicle-treated group. Rebamipid e also suppressed gastric damage induced by HCl in a dose-dependent manner. A COX-2 inhibitor blocked the rebamipide-induced increase in mucosal PGE(2 ), and mucosal protection induced by rebamipide. The results indicate that rebamipide induces COX-2 expression, increases PGE(2) levels, and enhances gastric mucosal defense in a COX-2-dependent manner. Thus, COX-2 has an imp ortant role in the effects of rebamipide on gastric mucosal protection.