Effects of hydroxytryptamine on the lower esophageal sphincter in vivo. Evidence for multiple sites of action

Abstract

Intravenous administration of 5 hydroxytryptamine (5 HT) caused a dose dependent contraction in the lower esophageal sphincter in the opossum. The smallest dose of 5 HT which caused a detectable contraction of the sphincter was 0.5 μg/kg, and a maximal sphincter contraction was produced by a dose of 40 μg/kg. Methysergide converted the contractile effect of 5 HT to a dose dependent fall in the sphincter pressure; maximal inhibition of 77.2 ± 7.2% of the resting pressure occurred with a dose of 40 μg/kg. The inhibitory effect of 5 HT was antagonized by tetrodotoxin, 5 MeO DMT, and 5 HT tachyphylaxis. 5 MeO DMT enhanced 5 HT induced contraction of the sphincter. In the presence of 5 MeO DMT and methysergide, 5 HT still caused a brief contraction of the sphincter; this contraction appeared to be due to stimulation of postganglionic cholinergic neurons as it was antagonized by tetrodotoxin or atropine. Reserpinization caused enhancement of the sphincter contraction by 5 HT. In the reserpinized animals in the presence of methysergide, 5 HT caused a small initial contraction followed by prolonged inhibition; atropine antagonized the initial contraction, while inhibition was antagonized by 5 MeO DMT. These studies are consistent with the view that 5 HT exerts several different effects on the sphincter. 5 HT causes contraction of the sphincter by its direct action on the muscle and also by stimulation of cholinergic excitatory neurons. In addition, 5 HT inhibits the sphincter by stimulation of nonadrenergic inhibitory neurons.