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• W2050611568 abstract "The impact of G-protein expression on the coupling specificity of the human alpha(2B)-adrenergic receptor (alpha(2B)-AR) was studied in Sf9 cells. The alpha(2B)-AR was shown to activate both coexpressed G(s)- and G(i)-proteins in a [(35)S]GTPgammaS binding assay. Noradrenaline and the synthetic agonist UK14,304 were equally potent and efficacious in stimulating G(i) activation. At the effector level (adenylyl cyclase), both ligands stimulated cAMP production. In the presence of forskolin, the effects of the agonists were more complex. Noradrenaline stimulated cAMP production, while UK14,304 showed a biphasic concentration-response curve with inhibition of stimulated cAMP production at low agonist concentrations and further stimulation at high agonist concentrations. G(s) coexpression caused a monophasic stimulatory response with both ligands. Coexpression with G(i) resulted in a biphasic concentration-response curve for noradrenaline and a monophasic inhibition with UK14,304. Experiments with a panel of agonists demonstrated that the more efficacious an agonist is in stimulating cAMP production, the weaker is its ability to couple to inhibition of cAMP accumulation via exogenous G(i). To be able to explain the mechanistic consequences of dual G-protein coupling described above, we developed a mathematical model based on the hypothesis that an agonist induces different conformations of the receptor having different affinity for different G-proteins. The model reproduced the profiles seen in the concentration-response curves with G(s) and G(i) coexpression. The model predicts that the affinity of the receptor conformation for G-proteins as well as the availability of G-proteins will determine the ultimate response of the receptor." @default.
• W2050611568 created "2016-06-24" @default.
• W2050611568 creator A5000419083 @default.
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• W2050611568 date "2001-10-01" @default.
• W2050611568 modified "2023-09-27" @default.
• W2050611568 title "Role of G-protein availability in differential signaling by alpha 2-adrenoceptors 1 1Abbreviations: α2-AR, α2-adrenergic receptor; AC, adenylyl cyclase; GTPγS, guanosine 5′-O-(3-thiotriphosphate); IBMX, 3-isobutyl-1-methyl-xanthine; UK14,304, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine." @default.
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• W2050611568 doi "https://doi.org/10.1016/s0006-2952(01)00730-4" @default.
• W2050611568 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11543726" @default.
• W2050611568 hasPublicationYear "2001" @default.
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