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 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 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 reflect sequential binding to the different receptors.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|