ETHANOL EFFECTS ON CALCIUM CHANNELS AND NMDA RECEPTORS

乙醇对钙通道和 NMDA 受体的影响

• 批准号: 2043334
• 负责人: STEVEN W LESLIE
• 金额: $ 20.75万
• 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/2043334
• 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.

这个竞争性的延续项目将继续研究以下因素的影响： 急性和慢性乙醇给药对钙进入神经元的影响 准备工作。 实验的重点是研究以下因素的影响： 乙醇对 NMDA 刺激钙进入游离脑细胞的影响。 还将对二氢吡啶-（L-型）和w-芋螺毒素-进行研究 敏感（N 型和 L 型）钙通道及其与 NMDA 的相互作用 受体。 大脑中 NMDA 刺激的谷氨酸受体似乎 参与神经元发育、神经元发育等许多重要过程 毒性与学习和记忆。 我们和其他国家最近的研究 实验室表明，NMDA 受体介导的大脑过程 对乙醇的抑制高度敏感。 中描述的研究 该应用将表征 NMDA 刺激的敏感性 钙从已知的大脑区域进入分离的脑细胞 NMDA 受体的高、中、低密度。 此外， 乙醇对 NMDA 受体的抑制作用机制 通过研究关键调节位点（甘氨酸共激动剂）的作用来确定 位点、PCP 抑制位点、Mg++ 抑制位点和竞争性位点 受体位点）激活 NMDA 功能（通过研究钙进入）和 在存在和不存在乙醇的情况下受体结合。 最近的证据 表明相关神经元异常之间可能存在联系 胎儿酒精暴露以及 NMDA 数量或功能的改变 受体；因此，将进行研究以检查胎儿的影响 酒精暴露对 NMDA 刺激的钙进入分离解离的影响 神经元。 受体结合研究也将在大脑上进行 从胎儿酒精暴露的大鼠幼崽中分离出膜来研究其 对 NMDA 受体调节的影响。 最后将进行研究 检测成年大鼠慢性乙醇暴露对 NMDA-的影响 受体调节。