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

Abstract
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.
AuthorsK Barnett, C J Bell, W McKnight, M Dicay, K A Sharkey, J L Wallace
JournalAmerican journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 279 Issue 6 Pg. G1292-7 (Dec 2000) ISSN: 0193-1857 [Print] United States
PMID11093953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Isoenzymes
  • Thiophenes
  • DuP 697
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Pentagastrin
  • Indomethacin
  • Iodoacetamide
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Cyclooxygenase 2
  • Enzyme Inhibitors (pharmacology)
  • Gastric Acid (metabolism)
  • Gastric Mucosa (drug effects, metabolism)
  • Gastritis (chemically induced, metabolism)
  • Indomethacin (pharmacology)
  • Iodoacetamide
  • Isoenzymes (physiology)
  • Male
  • Pentagastrin (pharmacology)
  • Prostaglandin-Endoperoxide Synthases (physiology)
  • Rats
  • Rats, Wistar
  • Thiophenes (pharmacology)

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