Kirson Dean, Cornelison Garrett L, Philpo Ashley E, Todorovic Jelena, Mihic S John
Department of Neuroscience, Division of Pharmacology and Toxicology, Waggoner Center for Alcohol & Addiction Research, Institutes for Neuroscience and Cell & Molecular Biology, University of Texas at Austin, MC A4800, 2500 Speedway, Austin, TX 78712, USA.
Department of Neuroscience, Division of Pharmacology and Toxicology, Waggoner Center for Alcohol & Addiction Research, Institutes for Neuroscience and Cell & Molecular Biology, University of Texas at Austin, MC A4800, 2500 Speedway, Austin, TX 78712, USA.
Neuropharmacology. 2013 Dec;75:286-94. doi: 10.1016/j.neuropharm.2013.07.025. Epub 2013 Aug 21.
Taurine is an endogenous ligand acting on glycine receptors in many brain regions, including the hippocampus, prefrontal cortex, and nucleus accumbens (nAcc). These areas also contain low concentrations of zinc, which is known to potentiate glycine receptor responses. Despite an increasing awareness of the role of the glycine receptor in the rewarding properties of drugs of abuse, the possible interactions of these compounds with zinc has not been thoroughly addressed. Two-electrode voltage-clamp electrophysiological experiments were performed on α1, α2 α1β and α2β glycine receptors expressed in Xenopus laevis oocytes. The effects of zinc alone, and zinc in combination with other positive modulators on the glycine receptor, were investigated when activated by the full agonist glycine versus the partial agonist taurine. Low concentrations of zinc enhanced responses of maximally-effective concentrations of taurine but not glycine. Likewise, chelation of zinc from buffers decreased responses of taurine- but not glycine-mediated currents. Potentiating concentrations of zinc decreased ethanol, isoflurane, and toluene enhancement of maximal taurine currents with no effects on maximal glycine currents. Our findings suggest that the concurrence of high concentrations of taurine and low concentrations of zinc attenuate the effects of additional modulators on the glycine receptor, and that these conditions are more representative of in vivo functioning than effects seen when these modulators are applied in isolation.
牛磺酸是一种内源性配体，作用于包括海马体、前额叶皮质和伏隔核（nAcc）在内的许多脑区的甘氨酸受体。这些区域还含有低浓度的锌，已知锌可增强甘氨酸受体反应。尽管人们越来越意识到甘氨酸受体在滥用药物奖赏特性中的作用，但这些化合物与锌之间可能的相互作用尚未得到充分研究。对非洲爪蟾卵母细胞中表达的α1、α2、α1β和α2β甘氨酸受体进行了双电极电压钳电生理实验。研究了单独的锌以及锌与其他正向调节剂联合作用于甘氨酸受体时，由完全激动剂甘氨酸与部分激动剂牛磺酸激活时的效果。低浓度的锌增强了最大有效浓度牛磺酸的反应，但未增强甘氨酸的反应。同样，从缓冲液中螯合锌会降低牛磺酸介导的电流反应，但不会降低甘氨酸介导的电流反应。增强浓度的锌会降低乙醇、异氟烷和甲苯对最大牛磺酸电流的增强作用，而对最大甘氨酸电流没有影响。我们的研究结果表明，高浓度牛磺酸和低浓度锌同时存在会减弱其他调节剂对甘氨酸受体的作用，而且与单独应用这些调节剂时的效果相比，这些条件更能代表体内的功能情况。
