Muscarinic M2 receptors in acetylcholine-isoproterenol functional antagonism in human isolated bronchus

The muscarinic functional antagonism of isoproterenol relaxation and the contribution of muscarinic M2 receptors were examined in human isolated bronchus. In intact tissues, acetylcholine (ACh) precontraction decreased isoproterenol potency and maximal relaxation (−log EC50 shift = −1.49 ± 0.16 and Emax inhibition for 100 μM ACh = 30%) more than the same levels of histamine contraction. The M2receptor-selective antagonist methoctramine (1 μM) reduced this antagonism in ACh- but not histamine-contracted tissues. Similar results were obtained for forskolin-induced relaxation. After selective inactivation of M3 receptors with 4-diphenylacetoxy- N-(2-chloroethyl)piperadine hydrochloric acid (3…