Cholinergic agonist and antagonist interactions on motor nerve endings of the rat--evidence for the involvement of presynaptic receptors in the regulation of acetylcholine release.

The effects of atropine and oxotremorine on the amplitude of contraction and on the release of Ach from rat isolated diaphragm were examined. Atropine (14-112 microM) induced a dose-related increase in the amplitude of contractions, the effect being potentiated by neostigmine (10 and 100 nM) or by increasing the rate of nerve stimulation and was accompanied by no change in the twitch evoked by retrograde injection of Ach. Atropine (112 microM) depressed the post-tetanic twitch response in muscles incubated in nutrient solution containing or not non-paralyzing concentration of d-tubocurarine (1 nM). Atropine (28 and 56 microM) enhanced and d-tubocurarine (1 nM) reduced the carbachol-induced neuromuscular facilitation. Atropine (28 and 56 microM) enhanced the evoked release of Ach, the effect being potentiated by increasing the rate of nerve stimulation. Oxotremorine (5-20 microM) inhibited the muscle contraction and depressed the evoked release of Ach. The effects were both prevented by atropine. The oxotremorine-induced blockade was potentiated by d-tubocurarine (1 nM), the effect being accompanied by no change in the twitch induced by retrograde injection of Ach. These results suggest the presence of muscarinic and nicotinic presynaptic receptors participating in a mechanism which might regulate the release of Ach.