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)
Salim
A S
AS
University Department of Surgery, Royal Infirmary, Glasgow, United Kingdom.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014628:Vagotomy
D012702:Serotonin Antagonists; D012701:Serotonin; D001285:Atropine; D002927:Cimetidine; D012110:Reserpine; D008784:Methysergide