Prejunctional muscarinic receptors modulating acetylcholine release in rabbit detrusor smooth muscles

We investigated the presence and subtypes of functionally prejunctional rec eptors in cholinergic nerve endings of rabbit detrusor smooth muscle strips using high-performance liquid chromatography coupled with a microdialysis procedure. The effects of pretreatment with various drugs on acetylcholine (ACh) release and contractile responses induced by electrical field stimula tion were evaluated. Although atropine (a muscarinic nonselective antagonis t) and 4-DAMP (a muscarinic M-3 antagonist) did not influence the ACh relea se, they markedly reduced the contractile responses. Pirenzepine (M-1 antag onist) decreased ACh release and contractile responses. Methoctramine (M-2 antagonist) increased the ACh release, but did not influence to the contrac tile responses. These results suggest that the muscarinic receptors in the rabbit detrusor smooth muscle are heterogeneous, prejunctional facilitatory (M-1 receptors), and inhibitory (M-2 receptors) for ACh release and postju nctional M-3 receptors mediating contractile responses.