D. Spina et al., THE EFFECT OF ALLOSTERIC ANTAGONISTS IN MODULATING MUSCARINIC M(2)-RECEPTOR FUNCTION IN GUINEA-PIG ISOLATED TRACHEA, British Journal of Pharmacology, 112(3), 1994, pp. 901-905
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.