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- W2030687516 abstract "The bidirectional modulation of ligand binding to benzodiazepine receptors (BzR) by GABA (the GABA shift) has been widely used to predict ligand efficacy. The present study examined the effects of GABA and muscimol on [3H]Ro 15-4513 binding to diazepam-insensitive (DI) and diazepam-sensitive (DS) BzR. Neither GABA nor muscimol significantly altered [3H]Ro 15-4513 binding to DI in cerebellum, while both compounds inhibit [3H]Ro 15-4513 binding to cerebellar DS in a concentration-dependent fashion. The maximum reductions in [3H]Ro 15-4513 binding to cerebral cortical and hippocampal membranes elicited by GABA were comparable to those obtained in cerebellar DS, but significantly less than obtained with the full inverse agonist [3H]3-carbomethoxy-beta-carboline. The qualitatively different effect of GABAmimetics on [3H]Ro 15-4513 binding to DS and DI is not species specific since identical effects were obtained in rat and mouse brain. Based on previously established criteria, Ro 15-4513 can be classified as a GABA-neutral (antagonist) ligand at DI and GABA negative (inverse agonist) at other BzR. These findings suggest that GABAA receptor subunit composition determines not only ligand affinity but also ligand efficacy." @default.
- W2030687516 created "2016-06-24" @default.
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- W2030687516 date "1992-05-01" @default.
- W2030687516 modified "2023-10-18" @default.
- W2030687516 title "Ro 15-4513 binding to GABAA receptors: Subunit composition determines ligand efficacy" @default.
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- W2030687516 doi "https://doi.org/10.1016/0091-3057(92)90454-n" @default.
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