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Prejunctional M1 and postjunctional M3 muscarinic receptors in the circular muscle of the guinea-pig ileum

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Abstract

The effects of subtype-selective muscarinic receptor antagonists on electrically evoked release of acetylcholine and muscle contraction were compared in circular muscle preparations of the guinea-pig ileum. Incubation of the preparation with [3H]choline resulted in the formation of [3H]acetylcholine. Electrical stimulation caused the release of [3H]acetylcholine which was abolished by tetrodotoxin and omission of calcium from the medium. 5-Hydroxytryptamine (10 μM) and the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (300 μM) did not change acetylcholine release. The muscarinic antagonists pirenzepine (M1 selective), AF-DX 116 (M2 selective) and hexahydrosiladifenidol (M3 selective) caused concentration-dependent increases in the evoked release of acetylcholine, and inhibitions of the circular muscle contraction. The postjunctional affinity constants (pA2 values) obtained for hexahydrosiladifenidol (8.06), pirenzepine (6.95) and AF-DX 116 (6.60) identified the muscular receptor as an M3 subtype. Pirenzepine was more potent in facilitating the evoked release than hexahydrosiladifenidol and AF-DX 116. These findings suggest that the release of acetylcholine in the circular muscle is inhibited by M1 muscarinic autoreceptors whereas muscle contraction is mediated by M3 receptors.

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Authors and Affiliations

  1. Department of Pharmacology, University of Mainz, Obere Zahlbacher Strasse 67, D-55101, Mainz, Germany

    C. Dietrich & H. Kilbinger

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  1. C. Dietrich
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  2. H. Kilbinger
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Dietrich, C., Kilbinger, H. Prejunctional M1 and postjunctional M3 muscarinic receptors in the circular muscle of the guinea-pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 351, 237–243 (1995). https://doi.org/10.1007/BF00233242

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  • DOI: https://doi.org/10.1007/BF00233242

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