Gastric acidification inhibits meal-stimulated gastric acid secretion after prostaglandin synthesis inhibition by indomethacin in humans.
The effects of cyclooxygenase inhibition by indomethacin on gastric acid secretion were studied in 8 healthy men. Oral doses of indomethacin (200 mg), administered 15 and 2 h before testing, were known to inhibit prostaglandin synthesis by 90% in 3 of the subjects as determined by prostaglandin E2 generation assay on endoscopically obtained gastric mucosal biopsy specimens. Acid-induced inhibition of gastric acid secretion was evaluated in a randomized and blinded study in which acid output was measured for 2 h during basal conditions by aspiration, for the next 2 h by intragastric titration during distention with isotonic glucose, and for the following 2 h by intragastric titration during meal stimulation with peptone. The studies were done on separate days, and intragastric pH was maintained at either 2.5 or 5.5 after administration of indomethacin or placebo. Basal acid output was not altered by indomethacin treatment. Distention of the stomach stimulated acid output significantly to a similar degree in all groups, without affecting plasma gastrin. Meal stimulation increased plasma gastrin and acid output significantly more at pH 5.5 (47 +/- 12 pM, 13 +/- 2 mmol/30 min) than at pH 2.5 (30 +/- 8 pM, 6 +/- 2 mmol/30 min). No effect of indomethacin treatment was observed. It is concluded that the participation of cyclooxygenase products in the mechanisms by which acid inhibits the gastric phase of acid secretion in humans is likely to be minor. These results also cast doubt on an important physiologic role for cyclooxygenase products in the regulation of basal acid secretion or of acid secretion stimulated by distention or a peptone meal.
D000328:Adult; D016861:Cyclooxygenase Inhibitors; D005502:Food; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010461:Peptones / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D005755:Gastrins; D010461:Peptones; D011451:Prostaglandin-Endoperoxide Synthases; D005947:Glucose; D007213:Indomethacin