Biochemical identification of the mammalian muscarinic cholinergic receptor

The muscarinic cholinergic antagonist 3 quinuclidinyl benzilate (QNB) binds avidly but reversibly to the muscarinic cholinergic receptor of mammalian brain and peripheral tissues. [³H]QNB binding provides a simple sensitive, specific assay for the muscarinic cholinergic receptor binding. Inhibition of [³H]QNB binding to homogenates of brain and guinea pig ileum by muscarinic drug correlates with their pharmacologic potencies, while nicotinic agents and noncholinergic drugs have negligible affinity. The regional distribution of [³H]QNB binding throughout rat and monkey brain parallels to a major extent cholinergic markers, suggesting that the majority of cholinergic synapses in the brain are muscarinic. [³H]QNB accumulation in various brain regions after intravenous injection provides a means of labeling the muscarinic receptor in vivo. By labeling the receptor in vivo, autoradiographic studies under the light microscope have been performed to visualize the muscarinic receptor.