Effects of in vitro ethanol and fetal ethanol exposure on glutathione stimulation of N-methyl-D-aspartate receptor function.
Effects of in vitro ethanol and fetal ethanol exposure on glutathione stimulation of N-methyl-D-aspartate receptor function.
复制标题
体外乙醇和胎儿乙醇暴露对谷胱甘肽刺激 N-甲基-D-天冬氨酸受体功能的影响。
DOI：
10.1111/j.1530-0277.1993.tb00812.x
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Leslie,SW
中科院分区：
文献类型：
--
作者：
Weaver,MS;Lee,YH;Morris,JL;Randall,PK;Schallert,T;Leslie,SW
本研究探讨了谷胱甘肽（GSH; γ-谷氨酰半胱氨酰甘氨酸）及其氧化形式（GSSG）对急性和慢性乙醇暴露制剂中神经元N-甲基-D-天冬氨酸（NMDA）受体激活的影响。使用来自新生大鼠幼仔的负载Fura-2的解离脑细胞证明，GSH和GSSG（0-4 mM）均产生与NMDA和其他NMDA受体激动剂产生的细胞内钙类似的浓度依赖性增加。GSH刺激的钙内流不受低浓度乙醇的抑制，这与乙醇对NMDA刺激的受体活化的典型抑制作用形成对比。成年大鼠的行为研究表明，在腹膜内注射20%（w/v）乙醇（3 g/kg）前约5 min，脑室内给予10 μl GSSG（20 mM），乙醇诱导的睡眠时间显著缩短。这些发现表明，乙醇对GSH刺激的钙离子内流的作用较弱，以及乙醇诱导的睡眠时间减少可能与肽中存在甘氨酸有关。谷胱甘肽中的甘氨酸可以激活甘氨酸位点，并阻断或减少乙醇对该位点的作用。看来，虽然GSH可能在NMDA受体的激活中发挥重要作用，但这种作用并不涉及对急性乙醇暴露敏感的过程。相比之下，当大鼠幼仔在fura-2制备前通过产前暴露长期暴露于乙醇时，NMDA和GSH刺激的钙内流增加相对于成对喂养和随意喂养的对照组显著降低。因此，子宫内长期暴露于乙醇可能会改变NMDA-受体复合物，从而显著降低NMDA或GSH激活介导的钙内流。
The present studies investigated the effects of glutathione (GSH; γ‐glutamylcysteinylglycine) and its oxidized form (GSSG) on neuronalN‐methyl‐D‐aspartate (NMDA) receptor activation in both acute and chronic preparations of ethanol exposure. It was demonstrated using fura‐2‐loaded dissociated brain cells from newborn rat pups that both GSH and GSSG (0–4 mM) produced concentration‐dependent increases in intracellular calcium similar to those produced by NMDA and other agonists of the NMDA receptor. GSH‐stimulated calcium entry was not inhibited by low intoxicating concentrations of ethanol, which contrasts with ethanol's typical inhibitory effect on NMDA‐stimulated receptor activation. Behavioral studies in adult rats demonstrated that ethanol‐induced sleep times were significantly decreased when 10 μl of GSSG (20 mM) were administered intracere‐broventricularly approximately 5 min before an intraperitoneal injection of 20% (w/v) ethanol (3 g/kg). These findings suggest that the less potent effect of ethanol on GSH‐stimulated calcium entry as well as the reduction in ethanol‐induced sleep times may be related to the presence of glycine in the peptide. The glycine found in GSH may activate the glycine site and block or reduce ethanol's action on this site. It appears that although GSH may play an important role in the activation of the NMDA receptor, this action does not involve a process that is sensitive to acute ethanol exposure. In contrast, when rat pups were chronically exposed to ethanol via prenatal exposure before the fura‐2 preparation, increases in NMDA‐ and GSH‐stimulated calcium entry were significantly decreased relative to those in pair‐fed and ad libitum‐fed controls. Thus, chronic in utero exposure to ethanol may alter the NMDA‐receptor complex, such that calcium entry mediated by NMDA or GSH activation is significantly reduced.