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Kinetic studies of [3H]-N-methylscopolamine binding to muscarinic receptors in the rat central nervous system: evidence for the existence of three classes of binding sites

M Waelbroeck, M Gillard, P Robberecht and J Christophe

We compared the binding of [N-methyl-3H]scopolamine methyl chloride [( 3H]NMS) and pirenzepine to muscarinic receptors in four regions of the rat central nervous system (cortex, hippocampus, striatum, and cerebellum) and in rat heart. Equilibrium binding studies suggested the existence of three classes of receptors: A, receptors with high affinity for pirenzepine and [3H] NMS (in cortex, hippocampus, and striatum); B, receptors with intermediate affinity for pirenzepine and high affinity for [3H]NMS (in the same brain regions); and C, receptors with low affinity for pirenzepine and [3H]NMS (in cerebellum and heart). Dissociation kinetic studies indicated that the receptor types A, B, and C had different koff values allowing, therefore, a separate study of their binding properties. We observed that: [3H]NMS recognized muscarinic receptors A, B, and C with the following order of potency: B greater than A much greater than C; and pirenzepine recognized these receptors with a different order of potency: A much greater than B greater than C. Thus, dissociation kinetics provide a useful tool to identify muscarinic receptor types.

Volume 30, Issue 4, pp. 305-314, 10/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1986 by the American Society for Pharmacology and Experimental Therapeutics