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. 1991 Apr;102(4):811–816. doi: 10.1111/j.1476-5381.1991.tb12257.x

Investigation of the 5-hydroxytryptamine receptor mechanism mediating the short-circuit current response in rat colon.

K T Bunce 1, C J Elswood 1, M T Ball 1
PMCID: PMC1917962  PMID: 1855112

Abstract

1. 5-Hydroxytryptamine (5-HT) stimulated an increase in short-circuit current (SCC) in rat isolated colonic mucosa with an EC50 value of approximately 4 microM. The purpose of the present study was to investigate the 5-HT receptor mechanism(s) involved in this response. 2. The relatively selective 5-HT receptor agonists 5-carboxamidotryptamine (5-CT) and alpha-methyl-5-HT stimulated SCC and were 6 to 8 times less potent than 5-HT. 2-Methyl-5-HT was inactive both as an agonist and an antagonist. 3. The following compounds produced no significant inhibition of the SCC response to 5-HT: ketanserin (1 microM), methysergide (1 microM), methiothepin (0.3 microM), GR38032F (0.3 microM), tetrodotoxin (0.3 microM) and sulpiride (1 microM). 4. Both metoclopramide (3 and 10 microM) and cisapride (0.1 and 1 microM) inhibited the SCC responses to 5-HT in a concentration-related manner, and the higher doses similarly inhibited the responses to 5-CT. With both agonists the inhibitory effects of metoclopramide and cisapride were insurmountable. However, these inhibitory actions appeared to be selective since neither metoclopramide nor cisapride affected the basal SCC or the SCC response to prostaglandin E2. 5. The SCC responses to 5-HT and 5-methoxytryptamine were selectively inhibited by ICS205-930 at 3 microM, and respective pKB values of 6.0 and 6.6 were calculated. 6. It is concluded that 5-HT stimulates an SCC response in rat colon via a receptor mechanism that cannot be clearly identified as 5-HT1-like, 5-HT2 or 5-HT3. This receptor is selectively antagonized by ICS 205-930 and by the benzamides, metoclopramide and cisapride.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Alphin R. S., Proakis A. G., Leonard C. A., Smith W. L., Dannenburg W. N., Kinnier W. J., Johnson D. N., Sancilio L. F., Ward J. W. Antagonism of cisplatin-induced emesis by metoclopramide and dazopride through enhancement of gastric motility. Dig Dis Sci. 1986 May;31(5):524–529. doi: 10.1007/BF01320319. [DOI] [PubMed] [Google Scholar]
  2. Apperley E., Humphrey P. P., Levy G. P. Receptors for 5-hydroxytryptamine and noradrenaline in rabbit isolated ear artery and aorta. Br J Pharmacol. 1976 Oct;58(2):211–221. doi: 10.1111/j.1476-5381.1976.tb10398.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baird A. W., Cuthbert A. W. Neuronal involvement in type 1 hypersensitivity reactions in gut epithelia. Br J Pharmacol. 1987 Nov;92(3):647–655. doi: 10.1111/j.1476-5381.1987.tb11368.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beubler E., Coupar I. M., Hardcastle J., Hardcastle P. T. Stimulatory effects of 5-hydroxytryptamine on fluid secretion and transmural potential difference in rat small intestine are mediated by different receptor subtypes. J Pharm Pharmacol. 1990 Jan;42(1):35–39. doi: 10.1111/j.2042-7158.1990.tb05345.x. [DOI] [PubMed] [Google Scholar]
  5. Bockaert J., Sebben M., Dumuis A. Pharmacological characterization of 5-hydroxytryptamine4(5-HT4) receptors positively coupled to adenylate cyclase in adult guinea pig hippocampal membranes: effect of substituted benzamide derivatives. Mol Pharmacol. 1990 Mar;37(3):408–411. [PubMed] [Google Scholar]
  6. Bradley P. B., Engel G., Feniuk W., Fozard J. R., Humphrey P. P., Middlemiss D. N., Mylecharane E. J., Richardson B. P., Saxena P. R. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology. 1986 Jun;25(6):563–576. doi: 10.1016/0028-3908(86)90207-8. [DOI] [PubMed] [Google Scholar]
  7. Branchek T. A., Gershon M. D. Development of neural receptors for serotonin in the murine bowel. J Comp Neurol. 1987 Apr 22;258(4):597–610. doi: 10.1002/cne.902580409. [DOI] [PubMed] [Google Scholar]
  8. Bunce K. T., Spraggs C. F. Stimulation of electrogenic chloride secretion by prostaglandin E2 in guinea-pig isolated gastric mucosa. J Physiol. 1988 Jun;400:381–394. doi: 10.1113/jphysiol.1988.sp017126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cassuto J., Jodal M., Tuttle R., Lundgren O. 5-hydroxytryptamine and cholera secretion. Physiological and pharmacological studies in cats and rats. Scand J Gastroenterol. 1982 Aug;17(5):695–703. doi: 10.3109/00365528209181081. [DOI] [PubMed] [Google Scholar]
  10. Clarke D. E., Craig D. A., Fozard J. R. The 5-HT4 receptor: naughty, but nice. Trends Pharmacol Sci. 1989 Oct;10(10):385–386. doi: 10.1016/0165-6147(89)90177-6. [DOI] [PubMed] [Google Scholar]
  11. Cooke H. J., Carey H. V. Pharmacological analysis of 5-hydroxytryptamine actions on guinea-pig ileal mucosa. Eur J Pharmacol. 1985 May 20;111(3):329–337. doi: 10.1016/0014-2999(85)90639-9. [DOI] [PubMed] [Google Scholar]
  12. Craig D. A., Clarke D. E. Pharmacological characterization of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-hydroxytryptamine receptor. J Pharmacol Exp Ther. 1990 Mar;252(3):1378–1386. [PubMed] [Google Scholar]
  13. Donowitz M., Binder H. J. Jejunal fluid and electrolyte secretion in carcinoid syndrome. Am J Dig Dis. 1975 Dec;20(12):1115–1122. doi: 10.1007/BF01070754. [DOI] [PubMed] [Google Scholar]
  14. Donowitz M., Charney A. N., Heffernan J. M. Effect of serotonin treatment on intestinal transport in the rabbit. Am J Physiol. 1977 Jan;232(1):E85–E94. doi: 10.1152/ajpendo.1977.232.1.E85. [DOI] [PubMed] [Google Scholar]
  15. Dumuis A., Sebben M., Bockaert J. The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons. Naunyn Schmiedebergs Arch Pharmacol. 1989 Oct;340(4):403–410. doi: 10.1007/BF00167041. [DOI] [PubMed] [Google Scholar]
  16. ERSPAMER V. Pharmacology of indole-alkylamines. Pharmacol Rev. 1954 Dec;6(4):425–487. [PubMed] [Google Scholar]
  17. Feniuk W., Humphrey P. P., Perren M. J., Watts A. D. A comparison of 5-hydroxytryptamine receptors mediating contraction in rabbit aorta and dog saphenous vein: evidence for different receptor types obtained by use of selective agonists and antagonists. Br J Pharmacol. 1985 Nov;86(3):697–704. doi: 10.1111/j.1476-5381.1985.tb08948.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gaginella T. S., Rimele T. J., Wietecha M. Studies on rat intestinal epithelial cell receptors for serotonin and opiates. J Physiol. 1983 Feb;335:101–111. doi: 10.1113/jphysiol.1983.sp014522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Humphrey P. P. Peripheral 5-hydroxytryptamine receptors and their classification. Neuropharmacology. 1984 Dec;23(12B):1503–1510. doi: 10.1016/0028-3908(84)90094-7. [DOI] [PubMed] [Google Scholar]
  20. Kenakin T. P. The classification of drugs and drug receptors in isolated tissues. Pharmacol Rev. 1984 Sep;36(3):165–222. [PubMed] [Google Scholar]
  21. Moriarty K. J., Higgs N. B., Woodford M., Warhurst G., Turnberg L. A. Inhibition of the effect of serotonin on rat ileal transport by cisapride: evidence in favour of the involvement of 5-HT2 receptors. Gut. 1987 Jul;28(7):844–848. doi: 10.1136/gut.28.7.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nelson D. R., Thomas D. R. [3H]-BRL 43694 (Granisetron), a specific ligand for 5-HT3 binding sites in rat brain cortical membranes. Biochem Pharmacol. 1989 May 15;38(10):1693–1695. doi: 10.1016/0006-2952(89)90319-5. [DOI] [PubMed] [Google Scholar]
  23. Racusen L. C., Binder H. J. Effect of prostaglandin on ion transport across isolated colonic mucosa. Dig Dis Sci. 1980 Dec;25(12):900–904. doi: 10.1007/BF01308038. [DOI] [PubMed] [Google Scholar]
  24. Scholtysik G. Evidence for inhibition by ICS 205-930 and stimulation by BRL 34915 of K+ conductance in cardiac muscle. Naunyn Schmiedebergs Arch Pharmacol. 1987 Jun;335(6):692–696. doi: 10.1007/BF00166988. [DOI] [PubMed] [Google Scholar]
  25. Thompson J. H. Serotonin and the alimentary tract. Res Commun Chem Pathol Pharmacol. 1971 Jul-Sep;2(4):687–781. [PubMed] [Google Scholar]
  26. Zimmerman T. W., Binder H. J. Serotonin-induced alteration of colonic electrolyte transport in the rat. Gastroenterology. 1984 Feb;86(2):310–317. [PubMed] [Google Scholar]

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