The effect of allosteric antagonists in modulating muscarinic M2-receptor function in guinea-pig isolated trachea.
1. We have assessed the influence of a range of synthetic cationic polypeptides with putative inhibitory actions at prejunctional muscarinic M2-receptors on electrical field stimulation-induced contraction of guinea-pig isolated tracheal preparations. Electrical field stimulation of epithelium-denuded guinea-pig trachea resulted in frequency-dependent contractile responses. As expected, tracheal smooth muscle sensitivity to electrical field stimulation was increased in tissues pretreated with the muscarinic M2-receptor antagonist, gallamine. In contrast, gallamine did not significantly alter the contractile potency to acetylcholine. 2. Unlike gallamine, the synthetic cationic polypeptides, poly-L-arginine, poly-L-lysine, poly-D-lysine, the cationic dye ruthenium red and the anionic polysaccharide, heparin, failed to increase significantly tracheal smooth muscle sensitivity to electrical field stimulation. 3. Poly-L-arginine, ruthenium red and heparin had no effect on the contractile response to exogenously applied methacholine. 4. These data are consistent with the concept that in guinea-pig tracheal smooth muscle, gallamine is an allosteric antagonist of guinea-pig tracheal muscarinic M2-receptors, whereas the various cationic polypeptides and the polyanion, heparin, are not.
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Department of Pharmacology, University of Western Australia, Nedlands.
Minshall
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Goldie
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D000494:Allosteric Regulation; D000818:Animals; D004558:Electric Stimulation; D004848:Epithelium / Q000502:physiology; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D011976:Receptors, Muscarinic; D012430:Ruthenium Red / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D010455:Peptides; D011976:Receptors, Muscarinic; D012430:Ruthenium Red; D005703:Gallamine Triethiodide