Pregnenolone sulfate and dehydroepiandrosterone sulfate inhibit GABA-gatedchloride currents in Xenopus oocytes expressing picrotoxin-insensitive GABA(A) receptors

We examined the effects of picrotoxinin, pregnenolone sulfate (PS) and dehy droepiandrosterone sulfate (DHEAS) on gamma-aminobutyric acid (GABA) respon ses in Xenopus oocytes injected with wild type alpha 1, beta 2 and gamma 2 GABA(A) receptor subunits and in oocytes injected with wild type alpha 1 an d beta 2 subunits and a mutated gamma 2 subunit that eliminates picrotoxin sensitivity. All three agents inhibited GABA currents in oocytes injected w ith wild type subunits. Oocytes injected with the mutated gamma 2 subunit s howed no inhibition of GABA responses by picrotoxinin at concentrations up to 100 mu M. PS and DHEAS inhibited GABA currents at similar concentrations in both sets of oocytes. These results indicate that PS and DHEAS do not r equire a functional picrotoxin site for inhibition of GABA responses. (C) 1 999 Elsevier Science Ltd. All rights reserved.