Effects of 5-hydroxytryptamine on the lower esophageal sphincter in vivo: evidence for multiple sites of action.
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 mug/kg, and a maximal sphincter contraction was produced by a dose of 40 mug/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 mug/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.
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004943:Esophagogastric Junction / Q000187:drug effects*; D008784:Methysergide / Q000494:pharmacology; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009893:Opossums; D010275:Parasympathetic Nervous System / Q000187:drug effects; D011312:Pressure; D011985:Receptors, Serotonin; D012110:Reserpine / Q000494:pharmacology; D011984:Sensory Receptor Cells; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists; D013618:Tachyphylaxis; D013779:Tetrodotoxin / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D008735:5-Methoxytryptamine; D013779:Tetrodotoxin; D012110:Reserpine; D008784:Methysergide
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