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• W2017457726 abstract "Altered gamma-aminobutyric acid (GABA)-ergic function is associated with neurological and psychiatric disorders. Certain progesterone metabolite 3alpha-hydroxy-5alpha-pregnan-20-one, or allopregnanolone (ALLO), increases the GABA-mediated chloride ion (Cl(-)) flux through GABA(A) receptors in a similar fashion as benzodiazepines and barbiturates. We have studied the effect of its 3beta diastereomer, 3beta-hydroxy-5alpha-pregnan-20-one, or isoallopregnanolone (ISO), on the Cl(-) flux and investigated the interaction between ISO and ALLO on GABA-mediated Cl(-) uptake in cortical homogenates from adult male Wistar rats. We found that ISO from 1 microM to 1 mM does not affect baseline Cl(-) uptake in rat cortical homogenates. Neither does ISO at dose range of 100 nM to 100 microM interact with 10 microM GABA in the Cl(-) uptake assay. In addition, ISO at the dose range of 1-30 microM does not affect flunitrazepam and pentobarbital-induced increase of Cl(-) uptake. We conclude that ISO selectively inhibits the ALLO-induced Cl(-) uptake with respect to ALLO concentrations. The IC(50) of ISO inhibition on 1 microM ALLO-induced Cl(-) uptake was calculated to be 12.25 microM. On the other hand, we have studied the effect of 30 microM ISO on ALLO (0.01 nM to 1 microM) induced displacement of tert-butylbicyclophosphorothionate (TBPS) binding. We did not note any interaction between ALLO and ISO on TBPS binding assay. These results indicate that ISO may be useful functional blocker of GABA(A) receptor potentiating steroid ALLO when used at concentrations that do not affect baseline GABAergic neurotransmission." @default.
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• W2017457726 date "2003-08-01" @default.
• W2017457726 modified "2023-10-18" @default.
• W2017457726 title "Allopregnanolone-stimulated GABA-mediated chloride ion flux is inhibited by 3β-hydroxy-5α-pregnan-20-one (isoallopregnanolone)" @default.
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• W2017457726 doi "https://doi.org/10.1016/s0006-8993(03)02939-1" @default.
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