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• W2397157059 endingPage "906" @default.
• W2397157059 startingPage "899" @default.
• W2397157059 abstract "We investigated whether alcuronium, an allosteric modulator of muscarinic acetylcholine receptors, can induce receptor-mediated activation of G_o proteins in liposomal membranes incorporating purified M₂ receptors and G_oproteins and whether its action is affected by the receptor/G_o protein (R/G_o) ratio. The binding of guanosine-γ-[³⁵S]thiotriphosphate ([³⁵S]GTPγS) served as the indicator of G protein activation. It was stimulated by empty receptors at high receptor densities, and the dose-response curve was shifted to the left by the agonist carbachol and to the right by the antagonist atropine. At an R/G_o ratio of 300:100, the rate of [³⁵S]GTPγS binding was the same in the presence or absence of 0.1 mm carbachol. Alcuronium increased the binding of [³⁵S]GTPγS at R/G_o ratios of <3:100 and diminished it at R/G_o ratios of >10:100, similar to previous observations on intact cells expressing muscarinic receptors at different densities. The apparent biphasicity of alcuronium action indicates that the allosteric modulator has at least two effects on muscarinic receptor/G protein interaction but its mechanistic basis is unclear. The “active state” of muscarinic receptors induced by alcuronium probably is different from that induced by carbachol. Changes in the densities of receptors and G_oproteins had little effect on the kinetics of [³⁵S]GTPγS binding and on receptor affinity for carbachol, provided the R/G_o ratio was kept constant. This suggests that the receptors and G proteins are located in microdomains in which their concentrations remain constant, despite variations in the amounts of lipidic membranes in the system." @default.
• W2397157059 created "2016-06-24" @default.
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• W2397157059 date "1998-11-01" @default.
• W2397157059 modified "2023-10-12" @default.
• W2397157059 title "Effects of an Agonist, Allosteric Modulator, and Antagonist on Guanosine-γ-[³⁵S]thiotriphosphate Binding to Liposomes with Varying Muscarinic Receptor/G_oProtein Stoichiometry" @default.
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• W2397157059 doi "https://doi.org/10.1124/mol.54.5.899" @default.
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