EFFECTS OF SELECTIVE CYCLOOXYGENASE-2 INHIBITORS ON ALKALINE SECRETORY AND MUCOSAL ULCEROGENIC RESPONSES IN RAT DUODENUM

Effects of the selective cyclooxygenase-2 (COX-2) inhibitors such as N S-398 and nimesulide on duodenal HCO3- secretory and ulcerogenic respo nses to mucosal acidification were examined in rats, in comparison wit h indomethacin, a nonselective COX inhibitor. Duodenal HCO3- secretion in anesthetized rats was increased in response to mucosal acidificati on. The increased HCO3- response to acid was significantly suppressed by pretreatment with indomethacin (10 mg kg(-1), s.c.), while both NS- 398 and nimesulide (10 mg kg(-1), s.c.) had no effect on this response . The luminal release of prostaglandin E2 (PGE2) was increased during and after mucosal acidification, and this response was significantly i nhibited by indomethacin but not NS-398 or nimesulide. Indomethacin pr ovoked hemorrhagic lesions in the duodenum when acid hypersecretion wa s concomitantly induced by histamine (8 mg kg(-1) hr(-1), i.v.), while either NS-398 or nimesulide did not cause damage in the duodenum. Eit her of these drugs had no effect on histamine-induced acid secretion. On the other hand, both NS-398 and nimesulide showed a significant sup pression against carrageenan-induced rat paw edema, similar to indomet hacin. The present study supports a mediator role for endogenous PGs i n duodenal HCO3- secretion in response to mucosal acidification and su ggests that COX-1 but not COX-2 is a key enzyme in regulating this pro cess and maintaining the mucosal integrity against acid in the duodenu m.