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.