Pharmacological and Ionic Characterizations of the Muscarinic Receptors Modulating [3H]Acetylcholine Release from Rat Cortical Synaptosomes’
0270.6474/85/0505-1202$02.00/O The Journal of Neuroscience CopyrIght 0 Society for Neuroscrence Vol. 5, No. 5, pp. 1202-1207 Printed in U.S.A. May 1985 Pharmacological and Ionic Characterizations of the Muscarinic Receptors Modulating [3H]Acetylcholine Release from Rat Cortical Synaptosomes’ EDWIN M. MEYER* AND DEBORAH H. OTERO Department of Pharmacology and Therapeutics, University of Florida School of Medicine, Gainesville, Florida 32610 Abstract brain (Gonzales and Crews, 1984). M,-receptors, however, appear pre- and postsynaptically in brain, are regulated by an intrinsic The muscarinic receptors that modulate acetylcholine membrane protein that binds to GTP (g-protein), and may not be release from rat cortical synaptosomes were characterized coupled to changes in phosphatidylinositol turnover. with respect to sensitivity to drugs that act selectively at M, The present studies were designed to determine whether M,- or or Ma receptor subtypes, as well as to changes in ionic Mp-receptors mediate the presynaptic modulation of ACh release. strength and membrane potential. The modulatory receptors These studies involve dose-response curves for the release of appear to be of the M2 type, since they are activated by synaptosomal [3H]ACh in the presence of selected muscarinic ago- carbachol, acetylcholine, methacholine, oxotremorine, and nists and antagonists, as well as treatments that selectively alter MI- bethanechol, but not by pilocarpine, and are blocked by or M,-receptor activity. Our results indicate that the presynaptic atropine, scopolamine, and gallamine (at high concentra- modulation of [3H]ACh release is mediated by MP- but not MI- tions), but not by pirenzepine or dicyclomine.
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