Flavonoid modulation of ionic currents mediated by GABA(A) and GABA(C) receptors.
The modulation of ionotropic gamma-aminobutyric acid (GABA) receptors (GABA-gated Cl(-) channels) by a group of natural and synthetic flavonoids was studied in electrophysiological experiments. Quercetin, apigenin, morine, chrysin and flavone inhibited ionic currents mediated by alpha(1)beta(1)gamma(2s) GABA(A) and rho(1) GABA(C) receptors expressed in Xenopus laevis oocytes in the micromolar range. alpha(1)beta(1)gamma(2s) GABA(A) and rho(1) GABA(C) receptors differ largely in their sensitivity to benzodiazepines, but they were similarly modulated by different flavonoids. Quercetin produced comparable actions on currents mediated by alpha(4)beta(2) neuronal nicotinic acetylcholine, serotonin 5-HT(3A) and glutamate AMPA/kainate receptors. Sedative and anxiolytic flavonoids, like chrysin or apigenin, failed to potentiate but antagonized alpha(1)beta(1)gamma(2s) GABA(A) receptors. Effects of apigenin and quercetin on alpha(1)beta(1)gamma(2s) GABA(A) receptors were insensitive to the benzodiazepine antagonist flumazenil. Results indicate that mechanism/s underlying the modulation of ionotropic GABA receptors by some flavonoids differs from that described for classic benzodiazepine modulation.
Goutman
Juan D
JD
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires) (INGEBI (CONICET-UBA)), Capital Federal (1428), Buenos Aires, Argentina.
Waxemberg
Maximiliano D
MD
Doñate-Oliver
Francisco
F
Pomata
Pablo E
PE
Calvo
Daniel J
DJ
D000818:Animals; D047310:Apigenin; D001571:Benzoflavones / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011794:Quercetin / Q000494:pharmacology; D018075:RNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014982:Xenopus laevis; D047309:Flavones
D047310:Apigenin; D001571:Benzoflavones; D005419:Flavonoids; D011794:Quercetin; D018075:RNA, Complementary; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; C087200:GABA-C receptor; C043561:chrysin; C011512:alpha-naphthoflavone; C008548:morin; D047309:Flavones