Presynaptic regulation by ACh of the NE mediated responses in the rat vas deferens

In the isolated electrically stimulated vas deferens preparation the effect of exogenous acetylcholine (ACh) was studied. It was possible to differentiate two separate sites for the action of ACh. A postsynaptic effect (M1) which is revealed as a sudden decrease in the basal tension of the muscular twitch, antagonized competitively by atropine (pA2 = 8.44 +/- 0.79), potentiated at a ratio of 10.24 by neostigmine, and not altered by hexamethonium, yohimbine, clonidine, theophylline or prazosin. Treatment with reserpine or 6-OH-DA induced a supersensitivity of this effect. The second action is a presynaptic effect (M2), which is manifested by a rapid increase in the muscular twitch, is dose-dependent to ACh, and is potentiated significantly by reserpine, neostigmine and clonidine. This latter effect was not modified by atropine, hexamethonium, yohimbine, prazosin or theophylline. The normal efficacy of ACh is 185 times greater in presynaptic over postsynaptic receptors. The increase in the twitch is not considered to be by the release of endogenous ACh or ATP. The evidence presented here indicates that the presynaptic effect of ACh (M2) is due to participation of alpha 2-adrenoceptors in enhancement of the release of norepinephrine (NE) from the nerve terminals.