The effect of allosteric antagonists in modulating muscarinic M₂‐receptor function in guinea‐pig isolated trachea

Abstract

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.

Eosinophil-induced release of acetylcholine from differentiated cholinergic nerve cells

“…However, the details of the mechanism of eosinophilassociated loss of function of M 2 receptors are not clear, particularly since a previous in vitro study using a synthetic cationic compound to mimic MBP failed to demonstrate loss of M 2 receptor function in guinea pig airways (30). We have recently published details of an in vitro model that simulates the interactions between eosinophils and cholinergic nerves (20,29).…”