title: Effects of 5-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 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.
mesh_terms: 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
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D008735:5-Methoxytryptamine; D013779:Tetrodotoxin; D012110:Reserpine; D008784:Methysergide
references.citation: J Clin Invest. 1973 Feb;52(2):337-41
references.pmid: 4346007
references.citation: Res Commun Chem Pathol Pharmacol. 1971 Jul-Sep;2(4):687-781
references.pmid: 4333835
references.citation: J Pharmacol Exp Ther. 1971 Aug;178(2):311-24
references.pmid: 4398295
references.citation: Acta Physiol Scand. 1971 Sep;83(1):115-23
references.pmid: 4398477
references.citation: J Pharmacol Exp Ther. 1973 Jun;185(3):530-9
references.pmid: 4712649
references.citation: J Clin Invest. 1973 Sep;52(9):2264-71
references.pmid: 4727458
references.citation: Am J Physiol. 1973 Dec;225(6):1265-70
references.pmid: 4760438
references.citation: Gastroenterology. 1968 Mar;54(3):453-6
references.pmid: 4868348
references.citation: Pharmacol Rev. 1966 Jun;18(2):997-1049
references.pmid: 5328391
references.citation: Ann Surg. 1970 Oct;172(4):585-94
references.pmid: 5458616
references.citation: J Pharmacol Exp Ther. 1968 Feb;159(2):243-9
references.pmid: 5638644
references.citation: J Pharmacol Exp Ther. 1968 Aug;162(2):270-6
references.pmid: 5666982
references.citation: Br J Pharmacol Chemother. 1968 Jul;33(3):480-92
references.pmid: 5728319
references.citation: J Clin Invest. 1969 Feb;48(2):408-19
references.pmid: 5764015
references.citation: Gut. 1965 Aug;6(4):338-42
references.pmid: 5829211
references.citation: Br J Pharmacol Chemother. 1957 Sep;12(3):323-8
references.pmid: 13460238
references.citation: Am J Med. 1957 Dec;23(6):886-93
references.pmid: 13487606
references.citation: Pharmacol Rev. 1961 Sep;13:399-439
references.pmid: 13710128
references.citation: Gut. 1961 Sep;2:252-62
references.pmid: 13879670
references.citation: Pharmacol Rev. 1962 Dec;14:531-50
references.pmid: 13988667
references.citation: Pharmacol Rev. 1963 Jun;15:225-76
references.pmid: 13994081
references.citation: Br J Pharmacol Chemother. 1963 Feb;20:150-70
references.pmid: 14025623
references.citation: Br J Pharmacol Chemother. 1963 Oct;21:306-22
references.pmid: 14081661
references.citation: Pharmacol Rev. 1964 Dec;16:341-80
references.pmid: 14240176
references.citation: Gut. 1966 Jun;7(3):208-16
references.pmid: 18668794
references.citation: J Clin Invest. 1975 May;55(5):1119-26
references.pmid: 164484
references.citation: Gastroenterology. 1976 Apr;70(4):516-22
references.pmid: 1254137
references.citation: Gastroenterology. 1976 Jul;71(1):62-7
references.pmid: 1278651
references.citation: J Pharmacol Exp Ther. 1966 Jul;153(1):70-80
references.pmid: 4288397
references.citation: Adv Pharmacol. 1968;6(Pt A):323-33
references.pmid: 4298803
references.citation: Br J Pharmacol Chemother. 1967 Mar;29(3):259-79
references.pmid: 4382740