Antagonism of beta-adrenoceptor-mediated relaxations of human bronchial smooth muscle by carbachol.

Activation of muscarinic M2 receptors has been suggested to account, in part, for the reduced relaxant potency of beta-adrenoceptor agonists in canine and guinea-pig tracheal smooth muscle pre-contracted with muscarinic agonists as compared to histamine. The aim of the present study was to determine whether the potency of isoprenaline is reduced in human bronchial ring preparations pre-contracted with carbachol as compared to histamine and whether activation of muscarinic M2 receptors contributes to this effect. Cumulative concentration-effect curves to isoprenaline were obtained in the absence and presence of muscarinic M2 receptor antagonism by methoctramine (0.3 microM) in bronchial ring preparations pre-contracted to equivalent isometric tensions with either histamine (10 microM) or carbachol (1 microM). The relaxant potency of isoprenaline was reduced in preparations pre-contracted with carbachol compared to histamine, but there was no significant effect of muscarinic M2 receptor antagonism on either the potency or maximal relaxation by isoprenaline. In conclusion, increased functional antagonism of beta-adrenoceptor-mediated relaxation by muscarinic agonists can be demonstrated in human bronchial smooth muscle, but muscarinic M2 receptors do not appear to contribute to this effect.