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Journal of Neuroscience, Vol 11, 3218-3226, Copyright © 1991 by Society for Neuroscience
Identification and localization of muscarinic acetylcholine receptor proteins in brain with subtype-specific antibodies
AI Levey, CA Kitt, WF Simonds, DL Price and MR Brann
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
mRNAs encoding five genetically distinct muscarinic ACh receptors are
present in the CNS. Because of their pharmacological similarities, it has
not been possible to detect the individual encoded proteins; thus, their
physiological functions are not well defined. To characterize the family of
proteins, a panel of subtype-selective antibodies was generated against
recombinant muscarinic receptor proteins and shown to bind specifically to
each of the cloned receptors. Using immunoprecipitation, three receptor
proteins (m1, m2, and m4) accounted for the vast majority of the total
solubilized muscarinic binding sites in rat brain. These receptor subtypes
had marked differences in regional and cellular localization as shown by
immunocytochemistry. The m1-protein was present in cortex and striatum and
was localized to cell bodies and neurites, consistent with its role as a
major postsynaptic muscarinic receptor. The m2-receptor protein was
abundant in basal forebrain, scattered striatal neurons, mesopontine
tegmentum, and cranial motor nuclei; this distribution is similar to that
of cholinergic neurons and suggests that m2 is an autoreceptor. However, m2
was also present in noncholinergic cortical and subcortical structures,
providing evidence that this subtype may presynaptically modulate release
of other neurotransmitters and/or function postsynaptically. The
m4-receptor was enriched in neostriatum, olfactory tubercle, and islands of
Calleja, indicating an important role in extrapyramidal function. These
results clarify the roles of these genetically defined receptor proteins in
cholinergic transmission in brain.(ABSTRACT TRUNCATED AT 250 WORDS)
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V. Bernard, O. Laribi, A. I. Levey, and B. Bloch
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