Evidence for the presence of function of the inhibitory M2 receptors in the rabbit airways and lungs.

We investigated to determine whether or not the inhibitory M2-receptors function in the rabbit lung and heart. Rabbits were anesthetized, vagotomized, paralyzed and ventilated. Administration of gallamine, an M2-receptor antagonist, augmented an increase of PT produced by vagal stimulation with or without simultaneous administration of histamine and the increases were dose-dependent. Conversely, prior treatment with pilocarpine, an M2-receptor agonist, reduced these responses in a dose-dependent manner. The PT responses to histamine injection only were not significantly altered by administration of either gallamine or pilocarpine. The remaining bronchoconstrictor responses to the three stimuli in the presence of gallamine or pilocarpine were completely blocked by atropine. In another series of experiments, gallamine treatment enhanced bronchoconstriction evoked by vagal stimulation but reduced acetylcholine (ACh)-induced bronchoconstriction. These opposite responses were dose-dependent for gallamine. The results suggest that there are inhibitory M2-receptors in the parasympathetic nerves innervating the lungs in the rabbit. Furthermore, gallamine treatment that completely blocked bradycardia evoked by ACh administration reduced vagally-mediated bradycardia. This implies that gallamine appears to have an antagonistic action on muscarinic receptors in the rabbit heart.