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• W2024383350 abstract "Recently, ring A reduced metabolites of naturally occurring steriods have been shown to act as allosteric modulators of GABA-gated chloride ion conductance. Specifically, 5α-pregnance-3α,21-diol-20-one (allotetrahydrodeoxycorticosterone; 5α-THDOC) was shown to be a positive allosteric effector. For example, 5α-THDOC enhances the specific binding of [3H]flunitrazepam, a benzodiazepine receptor agonist, among other pharmacological actions. Swim stress has been shown to reduce the ability of flurazepam, a prototypic benzodiazepine agonist, to antagonize the electrical precipitation of tonic hindlimb extension in mice. This stress-induced reduction in flurazepam's antiseizure efficacy persists for up to 72 h and is associated with alterations in the specific binding of ligands to the GABAA receptor complex. In the current study, the potentiation of [3H]flunitrazepam binding by 5α-THDOC was greater in cerebral cortical membranes prepared from stressed mice compared with unstressed controls. Moreover, nanomolar concentrations of 5α-THDOC that were ineffective in potentiating the specific binding of [35S]TBPS in cerebral cortical membranes prepared from unstressed control mice were capable of potentiating this binding in membranes prepared from stressed animals. Specifically, 50 nM 5α-THDOC caused a 23% increase in the specific binding of [35S]TBPS in membranes from stressed mice, whereas it was without any significant effect in unstressed controls. This apparent ability of 5α-THDOC to distinguish between the binding of [35S]TBPS to crude membranes prepared from stressed and unstressed control mice was eliminated in the presence of a 5 μM concentration of GABA. The data are consistent with an effect of stress on the ability of a GABA-positive steroid to allostetically modulate the binding of both a benzodiazepine agonist and GABAA-associated channel ligand. These data provide additional support for a stress-induced alteration of the GABAA receptor complex." @default.
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• W2024383350 title "Allosteric effects of a GABA receptor-active steroid are altered by stress" @default.
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• W2024383350 doi "https://doi.org/10.1016/0091-3057(94)90296-8" @default.
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