ETHANOL ON CALCIUM CHANNELS AND NMDA RECEPTORS

乙醇对钙通道和 NMDA 受体的影响

• 批准号: 3479893
• 负责人: STEVEN W LESLIE
• 金额: $ 19.95万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3479893
• 关键词: NMDA receptors; active sites; alcoholic beverage consumption; brain cell; calcium channel; calcium channel blockers; calcium flux; cell membrane; cerebellum; cerebral cortex; dihydropyridines; ethanol; fetal alcohol syndrome; glycine receptors; hippocampus; laboratory rat; magnesium; neuropharmacology; newborn animals; pregnancy; radiotracer; receptor binding; synaptosomes; voltage gated channel

This competing continuation project will continue to examine the effects of acute and chronic ethanol administration on calcium entry into neuronal preparations. The focus of the experiments will be to study the effects of ethanol on NMDA-stimulated calcium entry into dissociated brain cells. Studies will also be conducted on dihydropyridine-(L-type) and w-conotoxin- sensitive (N and L type) calcium channels and their interactions with NMDA receptors. NMDA-stimulated glutamate receptors in the brain appear to be involved in many important processes such as neuronal development, neuronal toxicity and learning and memory. Recent studies in our and other laboratories have shown that NMDA receptor-mediated processes in the brain are highly sensitive to inhibition by ethanol. The studies described in this application will characterize the sensitivity of NMDA-stimulated calcium entry into dissociated brain cells from brain regions known to have high, intermediate and low densities of NMDA receptors. Furthermore, mechanisms of ethanol's inhibitory effects on the NMDA receptor will be determined by studying the role of key modulatory sites (glycine co-agonist site, PCP-inhibitory site, Mg++ inhibitory site and the competitive receptor site) in activating NMDA function (by studying calcium entry) and receptor binding in the presence and absence of ethanol. Recent evidence suggests that there may be links between neuronal abnormalities associated with fetal alcohol exposure and alterations in number or function of NMDA receptors; thus, studies will be conducted to examine the effects of fetal alcohol exposure on NMDA-stimulated calcium entry into isolated dissociated neurons. Receptor binding studies will also be conducted on brain membranes isolated from fetal alcohol exposed rat pups to study its influence on NMDA-receptor modulation. Finally, studies will be conducted to examine the effects of chronic ethanol exposure in adult rats on NMDA- receptor modulation.

这一竞争性的延续项目将继续检查 急、慢性乙醇给药对神经元钙离子内流的影响 准备工作。实验的重点将是研究 乙醇对NMDA刺激的游离脑细胞钙内流的影响。 还将对二氢吡啶(L类)和W-芋螺毒素进行研究。 敏感(N和L型)钙通道及其与N-甲基-D-天冬氨酸的相互作用 感受器。NMDA刺激的大脑中的谷氨酸受体似乎是 参与许多重要的过程，如神经元发育、神经元 毒性、学习和记忆。我们和其他机构的最新研究 实验室已经表明，NMDA受体在大脑中介导的过程 对乙醇的抑制高度敏感。中描述的研究 这一应用将表征NMDA刺激的敏感性 钙从已知的脑区进入分离的脑细胞 高、中、低密度的NMDA受体。此外， 乙醇对NMDA受体的抑制作用机制如下 通过研究关键调节位点(甘氨酸共同激动剂)的作用而确定 位点、五氯苯酚抑制部位、镁离子抑制部位和竞争性 受体位置)激活NMDA功能(通过研究钙内流)和 在乙醇存在和不存在的情况下与受体结合。最近的证据 提示在神经元异常之间可能存在联系 胎儿酒精暴露和NMDA数量或功能的变化 因此，将进行研究以检查胎儿的影响 酒精暴露对NMDA刺激的钙离子内流的影响 神经元。受体结合研究也将在大脑上进行。 胎鼠酒精染毒幼鼠分离膜的实验研究 对NMDA受体调控的影响。最后，将进行研究 目的：研究慢性酒精暴露对成年大鼠NMDA的影响。 受体调节。