Two Types of Receptors for 5-hydroxytryptamine on the Cholinergic Nerves of the Guinea-pig Myenteric Plexus

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1985 Jun 1

PMID 3161573

Citations 18

Authors

H Kilbinger

Affiliations

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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.

Citing Articles

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References

Adam-Vizi V, Vizi E . Direct evidence of acetylcholine releasing effect of serotonin in the Auerbach plexus. J Neural Transm. 1978; 42(2):127-38. DOI: 10.1007/BF01675351. View

Szerb J . Storage and release of labelled acetylcholine in the myenteric plexus of the guinea-pig ileum. Can J Physiol Pharmacol. 1976; 54(1):12-22. DOI: 10.1139/y76-003. View

Drew G . Pharmacological characterization of the presynaptic alpha-adrenoceptors regulating cholinergic activity in the guinea-pig ileum. Br J Pharmacol. 1978; 64(2):293-300. PMC: 1668329. DOI: 10.1111/j.1476-5381.1978.tb17303.x. View

Birdsall N, BURGEN A, Hulme E . The binding of agonists to brain muscarinic receptors. Mol Pharmacol. 1978; 14(5):723-36. View

Costa M, Furness J . The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon. Br J Pharmacol. 1979; 65(2):237-48. PMC: 1668627. DOI: 10.1111/j.1476-5381.1979.tb07824.x. View

Wood J, Mayer C . Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel. J Neurophysiol. 1979; 42(2):582-93. DOI: 10.1152/jn.1979.42.2.582. View

Cerrito F, Raiteri M . Serotonin release is modulated by presynaptic autoreceptors. Eur J Pharmacol. 1979; 57(4):427-30. DOI: 10.1016/0014-2999(79)90506-5. View

Fozard J, Mobarok Ali A, Newgrosh G . Blockade of serotonin receptors on autonomic neurones by (-)-cocaine and some related compounds. Eur J Pharmacol. 1979; 59(3-4):195-210. DOI: 10.1016/0014-2999(79)90282-6. View

Huidobro-Toro J, 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; 61(4):335-45. DOI: 10.1016/0014-2999(80)90072-2. View

10.

North R, Henderson G, Katayama Y, Johnson S . Electrophysiological evidence for presynaptic inhibition of acetylcholine release by 5-hydroxytryptamine in the enteric nervous system. Neuroscience. 1980; 5(3):581-6. DOI: 10.1016/0306-4522(80)90055-x. View

11.

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):1331-40. DOI: 10.1016/0306-4522(80)90205-5. View

12.

Johnson S, Katayama Y, North R . Multiple actions of 5-hydroxytryptamine on myenteric neurones of the guinea-pig ileum. J Physiol. 1980; 304:459-70. PMC: 1282942. DOI: 10.1113/jphysiol.1980.sp013336. View

13.

Leysen J, Awouters F, Kennis L, Laduron P, Vandenberk J, Janssen P . Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci. 1981; 28(9):1015-22. DOI: 10.1016/0024-3205(81)90747-5. View

14.

Baumann P, Waldmeier P . Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn Schmiedebergs Arch Pharmacol. 1981; 317(1):36-43. DOI: 10.1007/BF00506254. View

15.

Wallis D . Neuronal 5-hydroxytryptamine receptors outside the central nervous system. Life Sci. 1981; 29(23):2345-55. DOI: 10.1016/0024-3205(81)90470-7. View

16.

Schlicker E, Gothert M . Antagonistic properties of quipazine at presynaptic serotonin receptors and alpha-adrenoceptors in rat brain cortex slices. Naunyn Schmiedebergs Arch Pharmacol. 1981; 317(3):204-8. DOI: 10.1007/BF00503817. View

17.

Gorich R, Weihrauch T, Kilbinger H . The inhibition by dopamine of cholinergic transmission in the isolated guinea-pig ileum. Mediation through alpha-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1982; 318(4):308-12. DOI: 10.1007/BF00501170. View

18.

Kilbinger H, Kruel R, 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; 319(3):231-8. DOI: 10.1007/BF00495871. View

19.

Martin L, Sanders-Bush E . The serotonin autoreceptor: antagonism by quipazine. Neuropharmacology. 1982; 21(5):445-50. DOI: 10.1016/0028-3908(82)90029-6. View

20.

Engel G, Gothert M, Muller-Schweinitzer E, Schlicker E, Sistonen L, Stadler P . 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; 324(2):116-24. DOI: 10.1007/BF00497016. View