THE EFFECT OF ALLOSTERIC ANTAGONISTS IN MODULATING MUSCARINIC M(2)-RECEPTOR FUNCTION IN GUINEA-PIG ISOLATED TRACHEA

1 We have assessed the influence of a range of synthetic cationic poly peptides with putative inhibitory actions at prejunctional muscarinic M(2)-receptors on electrical field stimulation-induced contraction of guinea-pig isolated tracheal preparations. Electrical field stimulatio n of epithelium-denuded guinea-pig trachea resulted in frequency-depen dent contractile responses. As expected, tracheal smooth muscle sensit ivity to electrical held stimulation was increased in tissues pretreat ed with the muscarinic M(2)-receptor antagonist, gallamine. In contras t, gallamine did not significantly alter the contractile potency to ac etylcholine, 2 Unlike gallamine, the synthetic cationic polypeptides, poly-L-arginine, poly-L-lysine, poly-D-lysine, the cationic dye ruthen ium red and the anionic polysaccharide, heparin, failed to increase si gnificantly tracheal smooth muscle sensitivity to electrical field sti mulation. 3 Poly-L-arginine, ruthenium red and heparin had no effect o n the contractile response to exogenously applied methacholine. 4 Thes e data are consistent with the concept that in guinea-pig tracheal smo oth muscle, gallamine is an allosteric antagonist of guinea-pig trache al muscarinic Mz-receptors, whereas the various cationic polypeptides and the polyanion, heparin, are not.