Assessment of selectivity of muscarinic antagonists for M1 and M2 receptors in rabbit isolated vas deferens.

Neurogenic contractions of the rabbit isolated vas deferens were inhibited by McN-A-343 but potentiated by carbachol. The actions of McN-A-343 and carbachol on the twitch contractions were antagonized to different degrees by antimuscarinic drugs: the affinity (pA2) of atropine and himbacine against McN-A-343 and carbachol was similar. However, pirenzepine and telenzepine displayed preferential antagonism of McN-A-343 responses, whereas the converse was true for methoctramine and AF-DX 116. The pA2 values of 6 antagonists against carbachol responses in rabbit vas deferens closely agree with those obtained in rat left atrium. In unstimulated organs carbachol and McN-A-343 had no effect on the resting tension. Contractions elicited by ATP, noradrenaline and KCl were potentiated by carbachol but were unaffected by McN-A-343. The data suggest the presence of a presynaptic M1 receptor mediating inhibition and a postsynaptic, cardiac-like M2 receptor enhancing neurogenic contractions in rabbit vas deferens.