MUSCARINIC RECEPTOR HETEROGENEITY IN RAT CENTRAL-NERVOUS-SYSTEM .1. BINDING OF 4 SELECTIVE ANTAGONISTS TO 3 MUSCARINIC RECEPTOR SUBCLASSES - A COMPARISON WITH M2 CARDIAC MUSCARINIC RECEPTORS OF THE C-TYPE

  • 1 July 1987
    • journal article
    • research article
    • Vol. 32  (1) , 91-99
Abstract
We previously observed that [3H]NMS recognizes three types of muscarinic receptors in rat brain (one M1 subclass with high affinity for pirenzepine, and two M2 subclasses with low affinities for pirenzepine), based on distinct affinity and kinetic constants of [3H]NMS for these three subclasses. In this work, we investigated the binding of four selective antagonists to these three (the M1 and two M2) subclasses. We were able to demonstrate that 1) cardiac-like M2 receptors with low affinity for pirenzepine and low affinity for N-methylscopolamine were present not only in cerebellum (as previously shown; see introduction) but also in cortex, striatum, and hippocampus, and 2) the two M2 receptor subclasses were discriminated by dicyclomine, 4-DAMP, and gallamine, as well as by AF-DX 116 and [3H]NMS. Our findings also suggested that the biphasic association and dissociation kinetics of [3H]NMS observed in various brain regions reflct sequential binding to the different receptors.