The existence of presynaptic autoreceptors modulating acetylcholine release from central cholinergic nerve endings was investigated by using rat hippocampal synaptosomes in a superfusion system. The presence of exogenous acetylcholine, carbachol or oxotremorine in the superfusion fluid produced a dose-dependent inhibition of the release of [3H]acetylcholine elicited by 15 mM KCl in synaptosomes prelabeled with tritiated choline. The inhibition was counteracted by atropine. Another well known muscarinic agonist, bethanechol, had no effect on [3H]acetylcholine release. Our results indicate that central cholinergic nerve terminals possess autoreceptors of the muscarinic type for the control of acetylcholine release. Moreover, differences seem to exist between pre-and postsynaptic muscarinic receptors in the central nervous system.
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