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. 1977 Jan;59(1):125–133. doi: 10.1172/JCI108609

Effects of 5-hydroxytryptamine on the lower esophageal sphincter in vivo: evidence for multiple sites of action.

S Rattan, R K Goyal
PMCID: PMC333339  PMID: 264287

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BROWNLEE G., JOHNSON E. S. THE SITE OF THE 5-HYDROXYTRYPTAMINE RECEPTOR ON THE INTRAMURAL NERVOUS PLEXUS OF THE GUINEA-PIG ISOLATED ILEUM. Br J Pharmacol Chemother. 1963 Oct;21:306–322. doi: 10.1111/j.1476-5381.1963.tb01529.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burks T. F. Mediation by 5-hydroxytryptamine of morphine stimulant actions in dog intestine. J Pharmacol Exp Ther. 1973 Jun;185(3):530–539. [PubMed] [Google Scholar]
  3. Bülbring E., Gershon M. D. Serotonin participation in the vagal inhibitory pathway to the stomach. Adv Pharmacol. 1968;6(Pt A):323–333. doi: 10.1016/s1054-3589(08)61188-6. [DOI] [PubMed] [Google Scholar]
  4. CLARK C. G., VANE J. R. The cardiac sphincter in the cat. Gut. 1961 Sep;2:252–262. doi: 10.1136/gut.2.3.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christensen J., Conklin J. L., Freeman B. W. Physiologic specialization at esophagogastric junction in three species. Am J Physiol. 1973 Dec;225(6):1265–1270. doi: 10.1152/ajplegacy.1973.225.6.1265. [DOI] [PubMed] [Google Scholar]
  6. Christensen J., Daniel E. E. Effects of some autonomic drugs on circular esophageal smooth muscle. J Pharmacol Exp Ther. 1968 Feb;159(2):243–249. [PubMed] [Google Scholar]
  7. Christensen J., Lund G. F. Esophageal responses to distension and electrical stimulation. J Clin Invest. 1969 Feb;48(2):408–419. doi: 10.1172/JCI105998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DAY M., VANE J. R. An analysis of the direct and indirect actions of drugs on the isolated guinea-pig ileum. Br J Pharmacol Chemother. 1963 Feb;20:150–170. doi: 10.1111/j.1476-5381.1963.tb01306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DiMarino A. J., Cohen S. The adrenergic control of lower esophageal sphincter function. An experimental model of denervation supersensitivity. J Clin Invest. 1973 Sep;52(9):2264–2271. doi: 10.1172/JCI107413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Drakontides A. B., Gershon M. D. 5-hydroxytryptamine receptors in the mouse duodenum. Br J Pharmacol Chemother. 1968 Jul;33(3):480–492. doi: 10.1111/j.1476-5381.1968.tb00496.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fillion G. M., Lluch S., Uvnäs B. Release of noradrenaline from the dog heart in situ after intravenous and intracoronary administration of 5-hydroxytryptamine. Acta Physiol Scand. 1971 Sep;83(1):115–123. doi: 10.1111/j.1748-1716.1971.tb05057.x. [DOI] [PubMed] [Google Scholar]
  12. Fishlock D. J., Parks A. G., Dewell J. V. Action of 5-hydroxytryptamine on the human stomach, duodenum, and jejunum in vitro. Gut. 1965 Aug;6(4):338–342. doi: 10.1136/gut.6.4.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. GADDUM J. H., PICARELLI Z. P. Two kinds of tryptamine receptor. Br J Pharmacol Chemother. 1957 Sep;12(3):323–328. doi: 10.1111/j.1476-5381.1957.tb00142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. GYERMEK L. 5-hydroxytryptamine antagonists. Pharmacol Rev. 1961 Sep;13:399–439. [PubMed] [Google Scholar]
  15. Gershon M. D. Effects of tetrodotoxin on innervated smooth muscle preparations. Br J Pharmacol Chemother. 1967 Mar;29(3):259–279. doi: 10.1111/j.1476-5381.1967.tb01958.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gershon M. D. Serotonin and the motility of the gastrointestinal tract. Gastroenterology. 1968 Mar;54(3):453–456. [PubMed] [Google Scholar]
  17. Goyal R. K., Rattan S. Genesis of basal sphincter pressure: effect of tetrodotoxin on lower esophageal sphincter pressure in opossum in vivo. Gastroenterology. 1976 Jul;71(1):62–67. [PubMed] [Google Scholar]
  18. Goyal R. K., Rattan S. Mechanism of the lower esophageal sphincter relaxation. Action of prostaglandin E 1 and theophylline. J Clin Invest. 1973 Feb;52(2):337–341. doi: 10.1172/JCI107189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Goyal R. K., Rattan S. Nature of the vagal inhibitory innervation to the lower esophageal sphincter. J Clin Invest. 1975 May;55(5):1119–1126. doi: 10.1172/JCI108013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Green R. D., 3rd, Fleming W. W., Schmidt J. L. Sensitivity changes in the isolated ileum of the guinea pig after pretreatment with reserpine. J Pharmacol Exp Ther. 1968 Aug;162(2):270–276. [PubMed] [Google Scholar]
  21. HENDRIX T. R., ATKINSON M., CLIFTON J. A., INGELFINGER F. J. The effect of 5-hydroxytryptamine on intestinal motor function in man. Am J Med. 1957 Dec;23(6):886–893. doi: 10.1016/0002-9343(57)90298-x. [DOI] [PubMed] [Google Scholar]
  22. Hudgins P. M., Fleming W. W. A relatively nonspecific supersensitivity in aortic strips resulting from pretreatment with reserpine. J Pharmacol Exp Ther. 1966 Jul;153(1):70–80. [PubMed] [Google Scholar]
  23. Kao C. Y. Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena. Pharmacol Rev. 1966 Jun;18(2):997–1049. [PubMed] [Google Scholar]
  24. Kellum J. M., Jaffe B. M. Validation and application of a radioimmunoassay for serotonin. Gastroenterology. 1976 Apr;70(4):516–522. [PubMed] [Google Scholar]
  25. Misiewicz J. J., Waller S. L., Eisner M. Motor responses of human gastrointestinal tract to 5-hydroxytryptamine in vivo and in vitro. Gut. 1966 Jun;7(3):208–216. doi: 10.1136/gut.7.3.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. PAINTAL A. S. EFFECTS OF DRUGS ON VERTEBRATE MECHANORECEPTORS. Pharmacol Rev. 1964 Dec;16:341–380. [PubMed] [Google Scholar]
  27. Reichle F. A., Brigham M. P., Reichle R. M., Rosemond G. P. The effect of gastrectomy on serotonin metabolism in the human portal vein. Ann Surg. 1970 Oct;172(4):585–594. doi: 10.1097/00000658-197010000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Robinson R. G., Gershon M. D. Synthesis and uptake of 5-hydroxytryptamine by the myenteric plexus of the guinea-pig ileum. A histochemical study. J Pharmacol Exp Ther. 1971 Aug;178(2):311–324. [PubMed] [Google Scholar]
  29. SHORE P. A. Release of serotonin and catecholamines by drugs. Pharmacol Rev. 1962 Dec;14:531–550. [PubMed] [Google Scholar]
  30. TRENDELENBURG U. Supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol Rev. 1963 Jun;15:225–276. [PubMed] [Google Scholar]
  31. Thompson J. H. Serotonin and the alimentary tract. Res Commun Chem Pathol Pharmacol. 1971 Jul-Sep;2(4):687–781. [PubMed] [Google Scholar]

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