Role of cyclooxygenase-2 in modulating gastric acid secretion in the normal and inflamed rat stomach.
Nonsteroidal anti-inflammatory drugs elevate gastric acid secretion, possibly contributing to their ability to interfere with gastric ulcer healing. Inhibitors of cyclooxygenase-2 have been shown to delay experimental gastric ulcer healing. In the present study, we tested the hypothesis that cyclooxygenase-2-derived prostaglandins modulate gastric acid secretion. Studies were performed in normal rats and in rats with iodoacetamide-induced gastritis. Inflammation in the latter group was confirmed histologically and by a threefold increase in tissue levels of the granulocyte marker myeloperoxidase and was also associated with overexpression of cyclooxygenase-2 in the stomach. Basal acid secretion in both groups of rats was not affected by pretreatment with DuP-697, a selective inhibitor of cyclooxygenase-2. A nonselective cyclooxygenase inhibitor, indomethacin, had no effect on acid secretion 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 either group of rats. Gastritis itself was associated with significantly increased 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 cyclooxygenase-1, not cyclooxygenase-2, exert inhibitory effects on acid secretion.
Barnett
K
K
Mucosal Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1 Canada.
Bell
C J
CJ
McKnight
W
W
Dicay
M
M
Sharkey
K A
KA
Wallace
J L
JL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005756:Gastritis / Q000139:chemically induced / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007460:Iodoacetamide; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D013876:Thiophenes; C064874:DuP 697; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010418:Pentagastrin; D007213:Indomethacin; D007460:Iodoacetamide