CIS-METHYLDIOXOLANE SPECIFICALLY RECOGNIZES THE M2 MUSCARINIC RECEPTOR

cis-Methyldioxolane (CD) is a muscarinic receptor agonist. [H-3]CD has been used to label a subpopulation of muscarinic receptors described as exhibiting high agonist affinity. Pharmacological evidence suggests that the population of receptors labeled by [H-3]CD consists of m2 an d/or m4 subtypes; however, no studies have directly addressed the subt ype selectivity of [H-3]CD. The present study characterizes binding of this ligand to individual human receptor subtypes expressed in transf ected Chinese hamster ovary cells. Results indicate that [H-3]CD binds with high affinity only to Hm2 receptors but not to all Hm2 receptors . Twenty-eight percent of Hm2 receptors bound [H-3]CD with a K-D of 3. 5 +/- 0.5 nM. Binding was eliminated in the presence of guanosine 5'-O -(3-thiotriphosphate), indicating that the Hm2 receptors labeled by [H -3]CD are those that are associated with GDP-bound G protein. Binding of [H-3]CD by only a subpopulation of Hm2 receptors is in agreement wi th data generated from studies of [H-3]CD binding in mammalian brain. Because muscarinic receptors have been implicated to play a role in th e pathogenesis of both Alzheimer's and Parkinson's disease, as well as the neurotoxicity of organophosphorus compounds, knowledge of the bin ding specificity of the muscarinic agonist [H-3]CD should aid research in these areas.