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. 1985 Jun;85(2):529–539. doi: 10.1111/j.1476-5381.1985.tb08890.x

Two types of receptors for 5-hydroxytryptamine on the cholinergic nerves of the guinea-pig myenteric plexus.

H Kilbinger, I Pfeuffer-Friederich
PMCID: PMC1916583  PMID: 3161573

Abstract

The effects of 5-hydroxytryptamine (5-HT) on spontaneous and electrically-evoked release of [3H]-acetylcholine (ACh) from guinea-pig myenteric plexus preparations preincubated with [3H]-choline have been investigated in the absence of cholinesterase inhibitors. 5-HT caused a transient increase in spontaneous release and an inhibition of the electrically-evoked release of [3H]-ACh. The 5-HT-induced contractions of the longitudinal muscle were clearly related to the increase in spontaneous release. The inhibitory effect was not due to activation of alpha-adrenoceptors since it was also observed in the presence of tolazoline and on strips from reserpine-pretreated guinea-pigs. After desensitization of the excitatory 5-HT receptors with 5-HT or metoclopramide the effects of 5-HT on spontaneous [3H]-ACh release were largely reduced. A variety of established antagonists at neuronal 5-HT receptors (i.e. metitepine 0.1-1 microM; methysergide 1 microM; ketanserin 0.1-1 microM; MDL 72222 0.1 microM; tropacocaine 1 microM) failed to block the excitation. The inhibition by 5-HT of the electrically evoked [3H]-ACh release was competitively antagonized by metitepine (pA2 7.6) and methysergide (pA2 7.0) but not by ketanserin. Tachyphylaxis to the inhibitory action of 5-HT did not occur. The results suggest that the excitatory 5-HT receptor ('M'-receptor) differs in its pharmacological properties from other neuronal 5-HT receptors. The presynaptically located inhibitory receptor may roughly correspond to the 5-HT1 receptor subtype but probably differs from the 5-HT autoreceptor.

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Selected References

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  1. ARIUENS E. J., SIMONIS A. M. A MOLECULAR BASIS FOR DRUG ACTION. THE INTERACTION OF ONE OR MORE DRUGS WITH DIFFERENT RECEPTORS. J Pharm Pharmacol. 1964 May;16:289–312. doi: 10.1111/j.2042-7158.1964.tb07461.x. [DOI] [PubMed] [Google Scholar]
  2. Adám-Vizi V., Vizi E. S. Direct evidence of acetylcholine releasing effect of serotonin in the Auerbach plexus. J Neural Transm. 1978;42(2):127–138. doi: 10.1007/BF01675351. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. BULBRING E., CREMA A. Observations concerning the action of 5-hydroxytryptamine on the peristaltic reflex. Br J Pharmacol Chemother. 1958 Dec;13(4):444–457. doi: 10.1111/j.1476-5381.1958.tb00236.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baumann P. A., Waldmeier P. C. Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn Schmiedebergs Arch Pharmacol. 1981 Aug;317(1):36–43. doi: 10.1007/BF00506254. [DOI] [PubMed] [Google Scholar]
  6. Birdsall N. J., Burgen A. S., Hulme E. C. The binding of agonists to brain muscarinic receptors. Mol Pharmacol. 1978 Sep;14(5):723–736. [PubMed] [Google Scholar]
  7. Cerrito F., Raiteri M. Serotonin release is modulated by presynaptic autoreceptors. Eur J Pharmacol. 1979 Aug 15;57(4):427–430. doi: 10.1016/0014-2999(79)90506-5. [DOI] [PubMed] [Google Scholar]
  8. Costa M., Furness J. B. The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon. Br J Pharmacol. 1979 Feb;65(2):237–248. doi: 10.1111/j.1476-5381.1979.tb07824.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drew G. M. Pharmacological characterization of the presynaptic alpha-adrenoceptors regulating cholinergic activity in the guinea-pig ileum. Br J Pharmacol. 1978 Oct;64(2):293–300. doi: 10.1111/j.1476-5381.1978.tb17303.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Engel G., Göthert M., Müller-Schweinitzer E., Schlicker E., Sistonen L., Stadler P. A. Evidence for common pharmacological properties of [3H]5-hydroxytryptamine binding sites, presynaptic 5-hydroxytryptamine autoreceptors in CNS and inhibitory presynaptic 5-hydroxytryptamine receptors on sympathetic nerves. Naunyn Schmiedebergs Arch Pharmacol. 1983 Sep;324(2):116–124. doi: 10.1007/BF00497016. [DOI] [PubMed] [Google Scholar]
  11. Fozard J. R. MDL 72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1984 May;326(1):36–44. doi: 10.1007/BF00518776. [DOI] [PubMed] [Google Scholar]
  12. Fozard J. R., Mobarok ALI A. T. Blockade of neuronal tryptamine receptors by metoclopramide. Eur J Pharmacol. 1978 May 1;49(1):109–112. doi: 10.1016/0014-2999(78)90228-5. [DOI] [PubMed] [Google Scholar]
  13. Fozard J. R., Mobarok Ali A. T., Newgrosh G. Blockade of serotonin receptors on autonomic neurones by (-)-cocaine and some related compounds. Eur J Pharmacol. 1979 Nov 16;59(3-4):195–210. doi: 10.1016/0014-2999(79)90282-6. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Gintzler A. R., Musacchio J. M. Interaction between serotonin and morphine in the guinea-pig ileum. J Pharmacol Exp Ther. 1974 May;189(2):484–492. [PubMed] [Google Scholar]
  16. Görich R., Weihrauch T. R., Kilbinger H. The inhibition by dopamine of cholinergic transmission in the isolated guinea-pig ileum. Mediation through alpha-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1982 Mar;318(4):308–312. doi: 10.1007/BF00501170. [DOI] [PubMed] [Google Scholar]
  17. Huidobro-Toro J. P., Foree B. Dual agonist-antagonist effects of 5-hydroxytryptamine (5-HT) in the guinea pig ileum: evidence for a selective receptor desensitization effect. Eur J Pharmacol. 1980 Feb;61(4):335–345. doi: 10.1016/0014-2999(80)90072-2. [DOI] [PubMed] [Google Scholar]
  18. Johnson S. M., Katayama Y., North R. A. Multiple actions of 5-hydroxytryptamine on myenteric neurones of the guinea-pig ileum. J Physiol. 1980 Jul;304:459–470. doi: 10.1113/jphysiol.1980.sp013336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kilbinger H., Kruel R., Pfeuffer-Friederich I., Wessler I. The effects of metoclopramide on acetylcholine release and on smooth muscle response in the isolated guinea-pig ileum. Naunyn Schmiedebergs Arch Pharmacol. 1982 Jun;319(3):231–238. doi: 10.1007/BF00495871. [DOI] [PubMed] [Google Scholar]
  20. Kilbinger H., Wessler I. Inhibition by acetylcholine of the stimulation-evoked release of [3H]acetylcholine from the guinea-pig myenteric plexus. Neuroscience. 1980;5(7):1331–1340. doi: 10.1016/0306-4522(80)90205-5. [DOI] [PubMed] [Google Scholar]
  21. Leysen J. E., Awouters F., Kennis L., Laduron P. M., Vandenberk J., Janssen P. A. Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci. 1981 Mar 2;28(9):1015–1022. doi: 10.1016/0024-3205(81)90747-5. [DOI] [PubMed] [Google Scholar]
  22. Martin L. L., Sanders-Bush E. The serotonin autoreceptor: antagonism by quipazine. Neuropharmacology. 1982 May;21(5):445–450. doi: 10.1016/0028-3908(82)90029-6. [DOI] [PubMed] [Google Scholar]
  23. Middlemiss D. N. 8-Hydroxy-2-(di-n-propylamino) tetralin is devoid of activity at the 5-hydroxytryptamine autoreceptor in rat brain. Implications for the proposed link between the autoreceptor and the [3H] 5-HT recognition site. Naunyn Schmiedebergs Arch Pharmacol. 1984 Aug;327(1):18–22. doi: 10.1007/BF00504986. [DOI] [PubMed] [Google Scholar]
  24. North R. A., Henderson G., Katayama Y., Johnson S. M. Electrophysiological evidence for presynaptic inhibition of acetylcholine release by 5-hydroxytryptamine in the enteric nervous system. Neuroscience. 1980;5(3):581–586. doi: 10.1016/0306-4522(80)90055-x. [DOI] [PubMed] [Google Scholar]
  25. Paton W. D., Vizi E. S. The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. Br J Pharmacol. 1969 Jan;35(1):10–28. doi: 10.1111/j.1476-5381.1969.tb07964.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rama Sastry B. V., Cheng H. C. Dissociation constants of D- and L-lactoylcholines and related compounds at cholinergic receptors. J Pharmacol Exp Ther. 1972 Feb;180(2):326–339. [PubMed] [Google Scholar]
  27. Schlicker E., Göthert M. Antagonistic properties of quipazine at presynaptic serotonin receptors and alpha-adrenoceptors in rat brain cortex slices. Naunyn Schmiedebergs Arch Pharmacol. 1981 Nov;317(3):204–208. doi: 10.1007/BF00503817. [DOI] [PubMed] [Google Scholar]
  28. Szerb J. C. Storage and release of labelled acetylcholine in the myenteric plexus of the guinea-pig ileum. Can J Physiol Pharmacol. 1976 Feb;54(1):12–22. doi: 10.1139/y76-003. [DOI] [PubMed] [Google Scholar]
  29. VAN ROSSUM J. M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther. 1963;143:299–330. [PubMed] [Google Scholar]
  30. Wallis D. Neuronal 5-hydroxytryptamine receptors outside the central nervous system. Life Sci. 1981 Dec 7;29(23):2345–2355. doi: 10.1016/0024-3205(81)90470-7. [DOI] [PubMed] [Google Scholar]
  31. Wood J. D., Mayer C. J. Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel. J Neurophysiol. 1979 Mar;42(2):582–593. doi: 10.1152/jn.1979.42.2.582. [DOI] [PubMed] [Google Scholar]

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