Waggoner Center for Alcohol and Addiction Research, and Institute for Neuroscience, University of Texas at Austin, Austin, Texas, USA.
J Pharmacol Exp Ther. 2012 Jul;342(1):61-70. doi: 10.1124/jpet.112.191486. Epub 2012 Apr 3.
Taurine acts as a partial agonist at the glycine receptor (GlyR) in some brain regions such as the hippocampus, striatum, and nucleus accumbens. Ethanol, volatile anesthetics, and inhaled drugs of abuse are all known positive allosteric modulators of GlyRs, but their effects on taurine-activated GlyRs remain poorly understood, especially their effects on the high concentrations of taurine likely to be found after synaptic release. Two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes was used to compare the enhancing effects of ethanol, anesthetics, and inhalants on human homomeric α1-GlyR activated by saturating concentrations of glycine versus taurine. Allosteric modulators had negligible effects on glycine-activated GlyR while potentiating taurine-activated currents. In addition, inhaled anesthetics markedly enhanced desensitization rates of taurine- but not glycine-activated receptors. Our findings suggest that ethanol, volatile anesthetics, and inhalants differentially affect the time courses of synaptic events at GlyR, depending on whether the receptor is activated by a full or partial agonist.
牛磺酸在一些脑区（如海马体、纹状体和伏隔核）作为甘氨酸受体（GlyR）的部分激动剂发挥作用。乙醇、挥发性麻醉剂和吸入性滥用药物都是 GlyR 的已知正变构调节剂，但它们对牛磺酸激活的 GlyR 的影响仍知之甚少，尤其是在突触释放后可能存在高浓度牛磺酸的情况下。利用非洲爪蟾卵母细胞的双电极电压钳电生理学，比较了乙醇、麻醉剂和吸入剂对人类同源α1-GlyR 的增强作用，该受体由甘氨酸和牛磺酸的饱和浓度激活。变构调节剂对甘氨酸激活的 GlyR 几乎没有影响，而对牛磺酸激活的电流有增强作用。此外，吸入麻醉剂显著增加了牛磺酸而非甘氨酸激活的受体的脱敏速率。我们的发现表明，乙醇、挥发性麻醉剂和吸入性药物根据受体是否被完全激动剂或部分激动剂激活，对 GlyR 突触事件的时程产生不同的影响。
