title: Modulation of acetylcholine release in rat striatal slices by muscarinic receptors which do not desensitize.
abstract: Feedback modulation of release by acetylcholine itself has been demonstrated and is thought to operate via presynaptic autoreceptors. One of the aims of this study was to re-evaluate the existence of cholinergic autoreceptors in rat striatal slices and to characterize these receptors further. For this study, rat striatal slices were prelabelled with tritiated choline, perfused and stimulated by successive 2 min depolarizations with KCl or by a prolonged depolarization. Tritiated acetylcholine release induced by KCl was Ca(2+) dependent, insensitive to tetrodotoxine and proportional to the KCl concentration in the depolarization medium. In slices stimulated up to 7 times by 20 mM KCl for 2 min, depolarizations always released between 3 and 4% of the available tritiated acetylcholine; prolonged perfusion with 20 mM KCl led to a persistent release of the neurotransmitter. Exogenous cholinergic agonists (acetylcholine, carbachol) as well as physostigmine, inhibited depolarization induced release of tritiated acetylcholine, and their effects were antagonized by atropine. Pirenzepine, an M(1) antagonist, was about 100 times less potent than atropine in antgonizing the inhibitory effect of carbachol, whose effect was comparable in the presence or absence of tetrotoxine. The continuous administration of carbachol or acetylcholine inhibited tritiated acetylcholine release induced by two depolarizations 30 min apart or by and throughout a prolonged depolarization. Our results show that acetylcholine release from striatal nerve terminals is modulated through muscarinic receptors located on, or very close to the nerve terminals and that upon prolonged exposure to agonists these receptors do not desensitize.
authors.affiliation: Unité de Pharmacologie Neuroimmunoendocrinienne, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Prado de Carvalho