Pre- and post-synaptic muscarinic receptors of the rat vas deferens: an update

The pre- and post-synaptic muscarinic receptors of the rat vas deferens are not M1 since the M1-selective antagonist pirenzepine (PZ) has low affinity for both. On this basis both the pre- and post-synaptic actions of ACh in this preparation seem to be mediated via M2-like muscarinic receptors. The following experimental observations reveal that both responses are mediated by pharmacologically distinct muscarinic receptors. The rank order of potency displayed by 3 muscarinic antagonists (Atropine, N-methyl-scopolamine [NMS] and PZ) at each of these sites is different. Atropine and PZ are selective blockers of the post-synaptic smooth muscle muscarinic receptor. NMS is a selective antagonist of the pre-synaptic muscarinic receptor that facilitates norepinephrine's release. Finally, PZ and NMS are non-competitive and competitive antagonists, post- and pre-synaptically, respectively. The results suggest that the post-synaptic smooth muscle muscarinic receptor belongs to the M2B (or M3) subtypes. The pre-synaptic muscarinic receptor belongs to the M2A (or M2) subtypes or to a subclass of the M2B (or M3) muscarinic receptor subtypes.