title: Gamma subunit dependent modulation by nitric oxide (NO) in recombinant GABAA receptor.
abstract: The effect of nitric oxide (NO) on GABA induced Cl- current of recombinant GABAA receptors was studied. Either alpha 1 beta 2 gamma 2s or alpha 1 beta 2 subunit mRNAs synthesized from cDNA of mouse brain were injected into Xenopus oocytes and functional GABAA receptors were expressed. GABA-induced Cl- current was measured with the two electrode voltage clamp technique. The NO donor NOC-18 reduced the GABA-induced Cl- current in the alpha 1 beta 2 gamma 2s subunit receptor in a dose-dependent manner. In alpha 1,beta 2 subunit receptor, NOC-18 had no effects on GABA-induced currents at low concentrations but showed potentiation at high concentration. These effects were antagonized by the NO extinguisher, carboxy-PTIO. The cGMP analogue 8-Br-cGMP failed to induce NO-like effects. NO directly acts at the GABAA receptor and the gamma 2s subunit is involved in its action.
authors.affiliation: Department of Anesthesiology, Osaka University Medical School, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukami
authors.forename: I
authors.initials: I
authors.lastname: Uchida
authors.forename: T
authors.initials: T
authors.lastname: Mashimo
authors.forename: M
authors.initials: M
authors.lastname: Takenoshita
authors.forename: I
authors.initials: I
authors.lastname: Yoshiya
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000737:chemistry*; D011994:Recombinant Proteins / Q000494:pharmacology; D014981:Xenopus
chemical_list: C093285:NOC 18; D009603:Nitroso Compounds; D010446:Peptide Fragments; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D009569:Nitric Oxide