Oligomeric structure of muscarinic receptors is shown by photoaffinity labeling: subunit assembly may explain high- and low-affinity agonist states.

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Abstract
The potent muscarinic photoaffinity reagent N-methyl-4-piperidyl p-azidobenzilate (azido-4NMPB) was used to covalently label specific muscarinic binding sites in various brain regions and in the heart. In the cortex and hippocampus, a single specifically labeled protein with an apparent MW of 86,000 daltons [d] was detected by gel electrophoresis. In the medulla pons, cerebellum and cardiac atria, there was a 160,000-d band in addition to the 86,000-d polypeptide. Under certain conditions, alkali or hyroxylamine treatment dissociated both macromolecules into a single 40,000-d polypeptide. Apparently, the muscarinic receptor exists in oligomeric forms and a dimer and tetramer of a basic 40,000-d peptide may exist as interconvertible species. A model is proposed to explain the biological architecture of the muscarinic receptors and a possible correlation between the azido-4NMPB-labeled polypeptide, and the 2 states of the receptor observed in agonist binding experiments is suggested.