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Structural Microheterogeneity of the Muscarinic Cholinergic Receptor Is Not Related to Functional Diversity Identified by Differences in Affinity for Pirenzepine
Author(s) -
Dadi H. K.,
Batteiger D.,
Keen M.,
Morris R. J.
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb13077.x
Subject(s) - pirenzepine , muscarinic acetylcholine receptor , cholinergic , muscarinic acetylcholine receptor m1 , neuroscience , receptor , chemistry , muscarinic acetylcholine receptor m2 , biology , biochemistry
The muscarinic receptor for acetylcholine shows a diversity in ligand binding properties and effector mechanisms which have suggested the existence of two subtypes (M 1 and M 2 ), to which the selective antagonist pirenzepine binds with markedly different affinities. The receptor from rat brain, covalently labelled with the alkylating antagonist tritiated propylbenzilylcholine mustard, displays a structural microheterogeneity on electrophoresis, covering the region of apparent molecular weight 66,000‐76,000, with dominant components at 68,000 and 73,000. Selective inhibition by pirenzepine of labelling of the M 1 receptor with tritiated mustard has been analysed on fluorographs of sodium dodecyl sulphate‐polyacrylamide gels and shown to cause a uniform reduction in radioactive labelling of the broad receptor peak, rather than selectively inhibiting either the high‐ or low‐molecular‐weight regions of the band. It is further shown that although this receptor microheterogeneity is found for each of four brain regions studied, it is not found for the heart receptor, which gives a discrete labelled band of apparent molecular weight 72,000. It is therefore suggested that the structural microheterogeneity is the result of tissue‐specific, posttranslational modification of the molecule, such as glycosylation, and is not directly related to the functional diversity of the receptor.