Departamento de Neurobiología Celular y Molecular, Laboratorio de Neurobiología Molecular y Celular I-II, Instituto de Neurobiología, Campus UNAM Juriquilla, Querétaro, Qro. México CP 76230.
ACS Chem Neurosci. 2012 Feb 15;3(2):96-104. doi: 10.1021/cn200083m. Epub 2011 Dec 9.
GABAρ1 receptors are highly expressed in bipolar neurons of the retina and to a lesser extent in several areas of the central nervous system (CNS), and dopamine and serotonin are also involved in the modulation of retinal neural transmission. Whether these biogenic amines have a direct effect on ionotropic GABA receptors was not known. Here, we report that GABAρ1 receptors, expressed in X. laevis oocytes, were negatively modulated by dopamine and serotonin and less so by octopamine and tyramine. Interestingly, these molecules did not have effects on GABA(A) receptors. 5-Carboxamido-tryptamine and apomorphine did not exert evident effects on any of the receptors. Schild plot analyses of the inhibitory actions of dopamine and serotonin on currents elicited by GABA showed slopes of 2.7 ± 0.3 and 6.1 ± 1.8, respectively, indicating a noncompetitive mechanism of inhibition. The inhibition of GABAρ1 currents was independent of the membrane potential and was insensitive to picrotoxin, a GABA receptor channel blocker and to the GABAρ-specific antagonist (1,2,5,6-tetrahydropyridine-4-yl)methyl phosphinic acid (TPMPA). Dopamine and serotonin changed the sensitivity of GABAρ1 receptors to the inhibitory actions of Zn(2+). In contrast, La(3+) potentiated the amplitude of the GABA currents generated during negative modulation by dopamine (EC(50) 146 μM) and serotonin (EC(50) 196 μM). The functional role of the direct modulation of GABAρ receptors by dopamine and serotonin remains to be elucidated; however, it may represent an important modulatory pathway in the retina, where GABAρ receptors are highly expressed and where these biogenic amines are abundant.
GABAρ1 受体在视网膜的双极神经元中高度表达，在中枢神经系统 (CNS) 的几个区域中表达程度较低，多巴胺和 5-羟色胺也参与了视网膜神经传递的调制。这些生物胺是否对离子型 GABA 受体有直接影响尚不清楚。在这里，我们报告说，在非洲爪蟾卵母细胞中表达的 GABAρ1 受体受多巴胺和 5-羟色胺的负调控，而受章鱼胺和酪胺的影响较小。有趣的是，这些分子对 GABA(A)受体没有影响。5-羧基酰胺色胺和阿扑吗啡对任何一种受体都没有明显作用。多巴胺和 5-羟色胺对 GABA 诱导电流的抑制作用的 Schild 作图分析表明，斜率分别为 2.7±0.3 和 6.1±1.8，表明抑制作用是非竞争性的。GABAρ1 电流的抑制与膜电位无关，对 GABA 受体通道阻断剂和 GABAρ 特异性拮抗剂（1,2,5,6-四氢吡啶-4-基）甲基膦酸（TPMPA）不敏感。多巴胺和 5-羟色胺改变了 GABAρ1 受体对 Zn(2+)抑制作用的敏感性。相比之下，La(3+)增强了多巴胺（EC(50)146 μM）和 5-羟色胺（EC(50)196 μM）负调控期间 GABA 电流的幅度。多巴胺和 5-羟色胺对 GABAρ 受体的直接调制的功能作用仍有待阐明；然而，它可能代表了视网膜中的一个重要调节途径，在那里 GABAρ 受体高度表达，并且这些生物胺丰富。
