Biochemical indentification of the mammalian muscarinic cholinergic receptor.

The muscarinic cholinergic antagonist 3-quinuclidinyl benzilate (QNB) binds avidly but reversibly to the muscarinic cholinergic recptor 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 drugs correlates with their pharmacologic potencies, while nicotinic agents and noncholinergic drugs have neglibible affinity. The regional distribution of [3H]QNB binding throughout rat and monkey brain parallels to a major extent other 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.