The Mechanism of Enantioselective Neurosteroid Actions on GABA_A Receptors.

ABSTRACT: The neurosteroid allopregnanolone (ALLO) and pregnanolone (PREG), are equally effective positive allosteric modulators (PAMs) of GABA_A receptors. Interestingly, the PAM effects of ALLO are strongly enantioselective, whereas those of PREG are not. This study was aimed at determining the basis for this difference in enantioselectivity. The oocyte electrophysiology studies showed that ent-ALLO potentiates GABA-elicited currents in α₁β₃ GABA_A receptors with lower potency and efficacy than ALLO, PREG or ent-PREG. The small PAM effect of ent-ALLO was prevented by the α₁(Q242L) mutation in the intersubunit neurosteroid binding site between the β₃ and α₁ subunits. Consistent with this result, neuroste

SUBMITTER: Tateiwa H 

PROVIDER: S-EPMC9953308 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature