Muscarinic cholinergic receptor localization in brain by electron microscopic autoradiography

Muscarinic cholinergic receptors were labeled by the potent, specific, irreversible muscarinic cholinergic antagonist propylbenzilylcholine mustard. Slices of rat hippocampus and cerebral cortex were labeled in vitro under conditions such that workable specific to non-specific ratios of receptor binding were obtained. Light microscopic autoradiography of 1 micrometer sections revealed a limited penetration of drug into the tissue and, by grain counts, confirmed the specific to non-specific ratios observed in preliminary biochemical studies. Examination of thin sections with the electron microscope revealed a significant fraction of (but not all) autoradiographic grains associated with synapses. This fraction was reduced in tissues coincubated with quinuclidinylbenzilate to produce blanks. These results indicate an enrichment of cholinergic muscarinic receptors at synapses.