CELLULAR MECHANISM OF OPIATE ACTION

阿片作用的细胞机制

• 批准号: 2012752
• 负责人: RICHARD J MILLER
• 金额: $ 10.03万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2012752
• 关键词: Adenoviridae; G protein; apoptosis; calcium channel; calcium flux; endogenous opioid; free radicals; glutamate receptor; laboratory rat; necrosis; neural inhibition; neurotransmitter transport; opioid receptor; potassium channel; protein structure function; pyramidal cells; sympathetic nervous system; synapses; tissue /cell culture; transfection /expression vector; voltage gated channel

The work detailed in this proposal is designed to elucidate the mechanisms by which opioid receptors regulate ion channels and synaptic communication.An associated aim is to understand the regulation of neuronal Ca signals in general and the role of Ca in determining the viability of neurons under normal and pathological conditions. The major areas of research will be: 1) What are the structures and properties of neuronal voltage sensitive Ca channels? How can these channels be regulated by opioid and other receptors? How do G-proteins participate in this process? How does this process contribute to the phenomenon of presynaptic inhibition? 2) How do opioid and other receptors regulate neuronal K channels? How are G-proteins involved in this process? How do these details differ from the regulation of Ca channels? 3)How are neuronal Ca signals regulated by opioid and other receptors? How do Ca and other intracellular mediators such as free radicals contribute to the death of neurons in different circumstances ? What are the relative roles of necrosis and apoptosis in these processes? These studies will involve the use of biophysical,biochemical and molecular biological techniques. It is hoped that this research will provide us with further information on the way that opioid drugs can regulate the activity of nerve cells.

本提案中详细介绍的工作旨在阐明机制 阿片受体调节离子通道和突触 交流的目的是了解 神经元CA信号通常，CA在确定 在正常和病理条件下神经元的生存力。专业 研究领域将是： 1）神经元敏感CA的结构和特性是什么 频道？这些渠道如何受阿片类药物和其他渠道的调节 受体？ G蛋白如何参与此过程？这是怎么回事 过程有助于突触前抑制的现象？ 2）阿片类药物和其他受体如何调节神经元K通道？怎样 G蛋白参与此过程？这些细节与 CA通道的调节？ 3）神经元CA信号如何受阿片类药物和其他受体调节？如何 DO CA和其他细胞内介体（例如自由基）贡献 在不同情况下神经元死亡？亲戚是什么 坏死和凋亡在这些过程中的作用？ 这些研究将涉及使用生物物理，生化和 分子生物技术。 希望这项研究能为我们提供有关的更多信息 阿片类药物可以调节神经细胞活性的方式。