Role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine-induced stimulation of H+ output in the rat. A new hypothesis for the mechanism of gastric acid secretion.

This study was undertaken in the rat to examine the role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine (0.1 mg/kg)-induced stimulation of gastric acid secretion. Reserpine significantly (p < 0.001) stimulated acid secretion relative to control values (197 +/- 3.1 vs 61 +/- 1.7 mumol, mean +/- SEM, n = 10). Atropine (5 mg/kg) and cimetidine (40 mg/kg) were equally effective in achieving a significant (p < 0.001) suppression of the reserpine-induced acid secretion (98 +/- 3.4 and 91 +/- 2.9 mumol, respectively, vs 197 +/- 3.1 mumol, mean +/- SEM, n = 10), an action intensified by administering them together, but not significantly so (84 +/- 5.3 mumol). Vagotomy was more effective (p < 0.001) than the latter combination in preventing acid stimulation by reserpine and allowed an acid output similar to that of vagotomy controls (14 +/- 1.2 vs 13 +/- 1.4 mumol, mean +/- SEM, n = 10). Dose dependent inhibition of the reserpine-induced stimulation of acid secretion was achieved by the 5-HT receptor antagonist methysergide, an inhibition significantly (p < 0.001) more effective than that afforded by vagotomy coupled with achlorhydria in 80% of animals was noted with the 5-20 mg/kg doses. Reserpine produces vagal adrenergic delivery to the stomach, which releases acid secretagogues and sensitizes parietal cells to them besides stimulating acid secretion, and 5-HT is discharged into the gastric mucosa by vagal adrenergic activity and by reserpine and liberates acid secretagogues by a paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS)