Summary
The effects of several muscarinic agonists on smooth muscle (postsynaptic effect) and on acetylcholine release (presynaptic effect) were compared in the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum.
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1.
For release experiments the acetylcholine stores of the preparation were labelled with 3H-choline. Electrical field stimulation in the absence of a cholinesterase inhibitor caused an outflow of tritium that reflected release of 3H-acetylcholine. The agonists oxotremorine, arecaidinepropargylester, methylfurmethide, muscarine, carbachol, arecoline and pilocarpine inhibited the stimulation-induced outflow in a concentration-dependent manner. At the highest concentrations used, the drugs depressed the evoked outflow by 83–96%. Scopolamine (10nM) antagonized the inhibitory effects of all agonists which suggests that the reduction of outflow was mediated by muscarine receptors.
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2.
Oxotremorine (100nM) depressed the twitch response to field stimulation at 0.1 Hz. The inhibitory effect was overcome by scopolamine (3nM). The twitch-inhibitory effect of oxotremorine is thought to result from stimulation of presynaptically located muscarine receptors.
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3.
All agonists contracted the longitudinal muscle in a concentration-dependent fashion. The rank orders of potencies for pre- and postsynaptic effects were dissimilar. Furthermore, the potency ratios (measured as EC 50 presynaptic: EC 50 postsynaptic) were not constant but varied from 0.37 (oxotremorine) to 2.9 (acetylcholine). The results suggest that pre-and postsynaptic muscarine receptors in the longitudinal muscle-myenteric plexus preparation differ slightly in their pharmacological properties.
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Kilbinger, H., Wessler, I. Pre- and postsynaptic effects of muscarinic agonists in the guinea-pig ileum. Naunyn-Schmiedeberg's Arch. Pharmacol. 314, 259–266 (1980). https://doi.org/10.1007/BF00498547
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DOI: https://doi.org/10.1007/BF00498547