Reserpine-induced post-receptor reduction in muscarinic-mediated airway smooth muscle contraction

Abstract

Radioligand binding was conducted on airways of the rat and human, surgically subdivided into trachea, lung airways, and parenchyma. 3H-QNB bound uniformly to receptors in separate sections of the rat and human airway. Receptor densities generally were ranked: lung airways > trachea > parenchyma. Receptor subtypes were identified mostly by pirenzepine displacement of bound 3H-QNB. The rat trachea, and rat and human lung airways had a uniformly low affinity for pirenzepine while rat and human parenchyma demonstrated both high and low affinity pirenzepine binding. Inhibition of methacholine-stimulated smooth muscle contraction by the M 1 receptor antagonist, pirenzepine, and M 2 receptor antagonist, gallamine, was studied in rat trachea and bronchus in vitro . Schild plot pA 2 values were compatible with low potency antagonism, thereby favoring the presence of M 3 receptors at these smooth muscle sites. Reserpine treatment of rats (0.5 mg kg −1 day −1 for 7 days) produced a decrease in peak tension in response to methacholine without changing the muscarinic receptor character (K d 3H-QNB), population density (B max in fmol mg −1 protein), or function (methacholine EC 50). These results indicate that muscarinic receptor heterogeneity exists in the airway of both laboratory rat and man. While the muscarinic receptor subserving airway smooth muscle contraction appears to be the M 3 subtype, decreased contractile responses to methacholine by trachea and bronchus from reserpine-treated rats were receptor independent.