Role of cyclooxygenase-2 in modulating gastric acid secretion in the normal and inflamed rat stomach

Nonsteroidal anti-inflammatory drugs elevate gastric acid secretion, possib ly contributing to their ability to interfere with gastric ulcer healing. I nhibitors of cyclooxygenase-2 have been shown to delay experimental gastric ulcer healing. In the present study, we tested the hypothesis that cycloox ygenase-2-derived prostaglandins modulate gastric acid secretion. Studies w ere performed in normal rats and in rats with iodoacetamide-induced gastrit is. Inflammation in the latter group was confirmed histologically and by a threefold increase in tissue levels of the granulocyte marker myeloperoxida se and was also associated with overexpression of cyclooxygenase-2 in the s tomach. Basal acid secretion in both groups of rats was not affected by pre treatment with DuP-697, a selective inhibitor of cyclooxygenase-2. A nonsel ective cyclooxygenase inhibitor, indomethacin, had no effect on acid secret ion in normal rats but caused a doubling of acid secretion in the rats with gastritis. DuP-697 had no effect on pentagastrin-induced secretion in eith er group of rats. Gastritis itself was associated with significantly increa sed pentagastrin-induced acid secretion, and this was further increased in rats pretreated with indomethacin. These results suggest that in a setting of gastric inflammation, prostaglandins derived from ocyclooxygenase-1, not cyclooxygenase-2, exert inhibitory effects on acid secretion.