Effect of indomethacin on basal and histamine stimulated human gastric acid secretion.

Abstract

SUMMARY The effect of acute administration of indomethacin over 24 hours on basal and histamine stimulated gastric acid secretion was evaluated in seven normal male volunteers. Augmented histamine tests (0.015 mg/kg/h) infused with the antihistamine diphenhydramine hydrochloride (25 mg/h) were performed before and after pretreatment with indomethacin or matching placebo capsules. The dose of indomethacin was 75 mg (sustained release capsules) taken 12 and 24 hours before and 50 mg taken one hour before a two hour histamine infusion test. Indomethacin enhanced basal gastric secretion from 3*5±0-5 to 6-4±0-6 mmol/h (p<0.01) and histamine stimulated secretion from 48±6 to 62±5 mmol/2 h (p<005). Indomethacin significantly inhibited systemic prostaglandin biosynthesis as measured by urinary excretion (87±12 vs 41±6 ng PGE/g creatinine/h) and the drug increased platelet aggregation time two, five, and six fold, respectively, induced by ADP, collagen, and adrenaline. The data indicate that therapeutic doses of indomethacin augmented basal and secretagogue stimulated gastric acid secretion in control subjects. The 15 August 1983 alterations or lack of alteration in gastric acid secretion after indomethacin therapy was predicted only from the knowledge of the inhibitory effect of the drug on prostaglandin biosynthesis.We undertook this study to evaluate the effect of indomethacin on basal and histamine stimulated gastric acid secretion in normal subjects. We used therapeutic concentrations of the drug and documented inhibition of systemic endogenous prostaglandin levels in the biological fluids of these control subjects. We found that indomethacin increased both basal and stimulated gastric acid secretion attributable to the drug.

Aspirin potentiates prestimulated acid secretion and mobilizes intracellular calcium in rabbit parietal cells.

“…We have shown that aspirin potentiates secretagogue-stimulated acid secretion in PC, as previously demonstrated for NSAIDs in vivo and in vitro (4)(5)(6)(7)(8). Several possibilities exist concerning the mechanisms by which aspirin affects stimulussecretion coupling and thereby potentiates PC function.…”

“…7). The decrease in PGE2 levels induced by aspirin could augment acid secretion in PC as we observed in the chambered frog gastric mucosa (37) and for indomethacin in vivo (5). However, in PC basal acid secretion was unaffected by this degree of reduction in PGE2 levels.…”

“…We and others have observed that salicylate and nonsalicylate nonsteroidal anti-inflammatory drugs (NSAIDs) stimulated basal acid secretion in vivo and potentiated histaminestimulated acid secretion in vivo and in vitro (4)(5)(6)(7)(8), suggesting that enhanced gastric acid secretion could play a role in the pathogenesis of NSAIDs-induced gastrointestinal mucosal injury.…”

Effect of histamine on gastric acid secretion “in vitro”: Interference with endogenous prostaglandins

“…This was supported by indirect studies employing different non-steroidal antiinflammatory agents (NSAIDs) as inhibitors of PGs generation, and by direct measurement of PGs production in the gastric juice or mucosal homogenates [2,3]. The finding that PGs may be synthesized by the gastric mucosa in response to secretory stimuli and exhibit an inhibitory action on gastric secretion suggests that endogenous PGs may locally modulate acid production by a negative feed-back mechanism.…”

Interactions between Antral Peptides and Prostaglandin Biosynthesis in Gastric Acid Regulation in Man

“…In a first series four tests were made in random order in each of 9 healthy male subjects with an aver age age of 31 (range [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] years and normal body weight. Plasma concentrations of somatostatin and gastrin, luminal somatostatinlike immunoreactivity.…”