title: Pregnenolone sulfate and dehydroepiandrosterone sulfate inhibit GABA-gated chloride currents in Xenopus oocytes expressing picrotoxin-insensitive GABA(A) receptors.
abstract: We examined the effects of picrotoxinin, pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS) on gamma-aminobutyric acid (GABA) responses in Xenopus oocytes injected with wild type alpha1, beta2 and gamma2 GABA(A) receptor subunits and in oocytes injected with wild type alpha1 and beta2 subunits and a mutated gamma2 subunit that eliminates picrotoxin sensitivity. All three agents inhibited GABA currents in oocytes injected with wild type subunits. Oocytes injected with the mutated gamma2 subunit showed no inhibition of GABA responses by picrotoxinin at concentrations up to 100 microM. PS and DHEAS inhibited GABA currents at similar concentrations in both sets of oocytes. These results indicate that PS and DHEAS do not require a functional picrotoxin site for inhibition of GABA responses.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: W
authors.initials: W
authors.lastname: Shen
authors.forename: S
authors.initials: S
authors.lastname: Mennerick
authors.forename: E C
authors.initials: EC
authors.lastname: Zorumski
authors.forename: D F
authors.initials: DF
authors.lastname: Covey
authors.forename: C F
authors.initials: CF
authors.lastname: Zorumski
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D005260:Female; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
chemical_list: D018118:Chloride Channels; D019314:Dehydroepiandrosterone Sulfate; D046911:Macromolecular Substances; D010852:Picrotoxin; D011284:Pregnenolone; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D005680:gamma-Aminobutyric Acid; C018370:pregnenolone sulfate