Goutman Juan D, Waxemberg Maximiliano D, Doñate-Oliver Francisco, Pomata Pablo E, Calvo Daniel J
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.
Eur J Pharmacol. 2003 Feb 14;461(2-3):79-87. doi: 10.1016/s0014-2999(03)01309-8.
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.
在电生理实验中研究了一组天然和合成黄酮类化合物对离子型γ-氨基丁酸（GABA）受体（GABA门控Cl(-)通道）的调节作用。槲皮素、芹菜素、桑色素、白杨素和黄酮在微摩尔范围内抑制了非洲爪蟾卵母细胞中表达的α(1)β(1)γ(2s) GABA(A)和ρ(1) GABA(C)受体介导的离子电流。α(1)β(1)γ(2s) GABA(A)和ρ(1) GABA(C)受体对苯二氮䓬类药物的敏感性差异很大，但它们受到不同黄酮类化合物的类似调节。槲皮素对由α(4)β(2)神经元烟碱型乙酰胆碱、5-羟色胺5-HT(3A)和谷氨酸AMPA/海人藻酸受体介导的电流产生类似作用。具有镇静和抗焦虑作用的黄酮类化合物，如白杨素或芹菜素，不能增强α(1)β(1)γ(2s) GABA(A)受体的作用，反而拮抗该受体。芹菜素和槲皮素对α(1)β(1)γ(2s) GABA(A)受体的作用对苯二氮䓬类拮抗剂氟马西尼不敏感。结果表明，一些黄酮类化合物对离子型GABA受体的调节机制与经典苯二氮䓬类调节机制不同。
