cis-Methyldioxolane specifically recognizes the m2 muscarinic receptor.
cis-Methyldioxolane (CD) is a muscarinic receptor agonist. [3H]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 [3H]CD consists of m2 and/or m4 subtypes; however, no studies have directly addressed the subtype selectivity of [3H]CD. The present study characterizes binding of this ligand to individual human receptor subtypes expressed in transfected Chinese hamster ovary cells. Results indicate that [3H]CD binds with high affinity only to Hm2 receptors but not to all Hm2 receptors. Twenty-eight percent of Hm2 receptors bound [3H]CD with a KD 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 [3H]CD are those that are associated with GDP-bound G protein. Binding of [3H]CD by only a subpopulation of Hm2 receptors is in agreement with data generated from studies of [3H]CD binding in mammalian brain. Because muscarinic receptors have been implicated to play a role in the pathogenesis of both Alzheimer's and Parkinson's disease, as well as the neurotoxicity of organophosphorus compounds, knowledge of the binding specificity of the muscarinic agonist [3H]CD should aid research in these areas.
Huff
R A
RA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Abou-Donia
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MB
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D004148:Dioxolanes / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007700:Kinetics; D010277:Parasympathomimetics / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*
D004148:Dioxolanes; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C024310:2-methyldioxolane; D011813:Quinuclidinyl Benzilate