TY - JOUR
T1 - Autoradiographic localization of M1 and M2 muscarine receptors in the rat brain
AU - Mash, D. C.
AU - Potter, L. T.
N1 - Funding Information:
Acknowledgements-The authorsa re indebtedt o Drs Can-date Pert and Miles Herkenhamf or their assistancea nd advicei n the initial stageso f this oroiect.W e wish to thank Dr Elliott Mufson for valuabled iscussionsa nd comments on them anuscriptL. eah Christiep rovidede xperts ecretarial assistancein preparingt he manuscript.T his study was supportedi n part by grantsf rom the National Parkinson F oundation and from the National Science Foundation (NS-07665).
PY - 1986/10
Y1 - 1986/10
N2 - The distribution of M1 and M2 muscarine receptors in the rat brain was investigated by in vitro autoradiography. Muscarine receptors were visualized after complete receptor uncoupling in ethylenediaminetetraacetic acid buffer containing 1 mM N-ethyl maleimide and saturation with the ligand [3H]quinuclidinyl benzilate. Pirenzepine, an M1-selective antagonist, was used in our assays as a counter ligand to occlude M1 sites, allowing the primary ligand, [3H]quinuclidinyl benzilate, to label the remaining M2 muscarine receptors. In adjacent sections, M1 muscarine receptors were labelled with [3H]quinuclidinyl benzilate in the presence of sufficient carbachol, an M2-selective agonist, to inhibit the binding to M2 sites. Our results reveal a heterogeneous distribution of M1 and M2 receptors. Increased densities of carbacholresistant and pirenzepine-sensitive sites (M1 receptor subtype) were apparent over many forebrain structures including the olfactory tubercle, caudate-putamen, nucleus accumbens, hippocampus, amygdala and cerebral cortex. In contrast, pirenzepine-resistant and carbachol-sensitive sites (M2 receptor subtype) were distributed throughout the brain with increased densities apparent over regions known to contain large numbers of cholinergic cell bodies. M2 receptor localization patterns were largely coincident with the regional distribution and intensity of acetylcholinesterase positive sites. Since the M2 receptor pattern appears to parallel regional innervation densities, we conclude that the M2 receptor may serve as a marker for cholinergic pathways. The findings also suggest that M1 muscarine receptors are involved in the presumptive postsynaptic actions of acetylcholine in many forebrain structures.
AB - The distribution of M1 and M2 muscarine receptors in the rat brain was investigated by in vitro autoradiography. Muscarine receptors were visualized after complete receptor uncoupling in ethylenediaminetetraacetic acid buffer containing 1 mM N-ethyl maleimide and saturation with the ligand [3H]quinuclidinyl benzilate. Pirenzepine, an M1-selective antagonist, was used in our assays as a counter ligand to occlude M1 sites, allowing the primary ligand, [3H]quinuclidinyl benzilate, to label the remaining M2 muscarine receptors. In adjacent sections, M1 muscarine receptors were labelled with [3H]quinuclidinyl benzilate in the presence of sufficient carbachol, an M2-selective agonist, to inhibit the binding to M2 sites. Our results reveal a heterogeneous distribution of M1 and M2 receptors. Increased densities of carbacholresistant and pirenzepine-sensitive sites (M1 receptor subtype) were apparent over many forebrain structures including the olfactory tubercle, caudate-putamen, nucleus accumbens, hippocampus, amygdala and cerebral cortex. In contrast, pirenzepine-resistant and carbachol-sensitive sites (M2 receptor subtype) were distributed throughout the brain with increased densities apparent over regions known to contain large numbers of cholinergic cell bodies. M2 receptor localization patterns were largely coincident with the regional distribution and intensity of acetylcholinesterase positive sites. Since the M2 receptor pattern appears to parallel regional innervation densities, we conclude that the M2 receptor may serve as a marker for cholinergic pathways. The findings also suggest that M1 muscarine receptors are involved in the presumptive postsynaptic actions of acetylcholine in many forebrain structures.
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U2 - 10.1016/0306-4522(86)90280-0
DO - 10.1016/0306-4522(86)90280-0
M3 - Article
C2 - 3774154
AN - SCOPUS:0022869345
VL - 19
SP - 551
EP - 564
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 2
ER -