Effect of celecoxib, a COX‐2 selective inhibitor, on duodenal HCO3‐ and ulcereogenic responses caused by mucosal acidification in rats (904.3)

Abstract

We examined the effect of celecoxib, a selective COX‐2 inhibitor, on duodenal HCO3‐ and ulcerogenic responses caused by acid in rats, in comparison with indomethacin and loxoprofen (nonselective COX inhibitors) or SC‐560 (a selective COX‐1 inhibitor). Methods: Male SD rats were used after 18 h fasting. Under urethane anesthesia, the duodenal loop was perfused with saline, and the HCO3‐ secretion was measured at pH 7.0 using a pH‐stat method. Results: Mucosal acidification (exposure to 10 mM HCl for 10 min) stimulated HCO3‐ secretion with an increase of mucosal PGE2 contents in the duodenum. These responses were significantly attenuated by pretreatment with indomethacin, loxoprofen or SC‐560, while celecoxib had no effect. Perfusion of the loop with 100 mM HCl for 4 h produced mild hemorrhagic damage, and the severity of these lesions was significantly aggravated by indomethacin, loxoprofen and SC‐560 but not celecoxib. COX‐2 was not expressed in the duodenal mucosa after acidification, while COX‐1 was expressed in the normal mucosa and remained unchanged after acid treatment. Conclusion: These results confirmed the importance of COX‐1 in the mechanism for the acid‐induced duodenal HCO3‐ secretion and further suggested that COX‐1/PGs play a crucial role in the protection of the duodenal mucosa against acid injury.