Role of cyclooxygenase isoforms in gastric mucosal defense and ulcer healing.

The rationale for the development of selective inhibitors of cyclooxygenase-2 (COX-2) was the proposal that this enzyme plays an important role in inflammation but does not contribute to the resistance of the gastrointestinal mucosa against injury. However, studies from several groups have established that both COX-1 and COX-2 have important functions in the maintenance of gastrointestinal mucosal integrity. Thus, in the normal rat stomach lesions only develop when both COX-1 and COX-2 are inhibited. On the other hand, in specific pathophysiological situations the isolated inhibition of either COX-1 or COX-2 without simultaneous suppression of the other COX isoenzyme is ulcerogenic. Furthermore, COX-2 plays an important role in the healing of gastric ulcers and inhibition of COX-2 delays ulcer healing. From these findings the initial concept that only inhibition of COX-1 interferes with gastrointestinal defense has to be re-evaluated.