Identification of the primary muscarinic autoreceptor subtype in rat striatum as m2 through a correlation of in vivo microdialysis and in vitro receptor binding data.
Muscarinic autoreceptors located on cholinergic nerve terminals are involved in the inhibitory feedback regulation of acetylcholine (ACh) release. Establishing the subtype identity of such sites provides a more complete understanding of both normal receptor function and the functional significance of receptor changes associated with various neurodegenerative diseases. In this study, a novel approach was used to identify the muscarinic autoreceptor in rat striatum. It involved the correlation of data from two different sources--in vivo microdialysis and in vitro receptor binding. Four standard muscarinic antagonists with varying binding profiles (scopolamine, pirenzepine, AF-DX116 and himbacine) were infused directly through a microdialysis probe into the striatum of conscious, freely moving rats. The objectives were to find the minimal concentration of each antagonist capable of manifesting a functional autoreceptor response (i.e., increased ACh release) and to compare the relative ability of the antagonists to bring about this effect with their relative abilities to bind to each of the cloned muscarinic receptor subtypes. The conclusion is that the muscarinic receptor mediating ACh release in rat striatum exhibits a pharmacological profile clearly consistent with it being of the m2 subtype.
Billard
W
W
Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
Binch
H
H
Crosby
G
G
McQuade
R D
RD
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D017660:Autoreceptors / Q000145:classification*; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000737:chemistry*; D008297:Male; D017551:Microdialysis; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000145:classification*
D017660:Autoreceptors; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine