MECHANISMS OF SYNAPTIC MODULATION IN SYMPATHETIC NEURONS

交感神经元突触调节机制

• 批准号: 2883641
• 负责人: MARK A. SIMMONS
• 金额: $ 14.79万
• 依托单位: MARSHALL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2883641
• 关键词: Rana; biological signal transduction; drug receptors; endocytosis; fluorescence microscopy; gonadotropin releasing factor; gonadotropins; hormone receptor; hormone regulation /control mechanism; molecular cloning; neuropeptide receptor; protein structure function; receptor binding; substance P; sympathetic nervous system; synapses

DESCRIPTION The nervous system operates by conducting impulses from one neuron to another by synaptic transmission. The essential events in synaptic transmission are the release of neurotransmitter from a presynaptic neuron and the binding of that neurotransmitter to receptor proteins on the membrane of a postsynaptic cell. This process of synaptic transmission is fundamental to the functioning of the nervous system. In addition to endogenous neurotransmitters, many exogenous compounds, including therapeutic and non-therapeutic agents, bind to neurotransmitter receptors and, thereby, alter neuronal function. In many situations, repeated or continuous exposure to drugs or neurotransmitters results in changes in the responsiveness of neurons to that drug or neurotransmitter. Frequently this change involves a decreased sensitivity to that drug. With therapeutic agents, this may be observed as the development of tolerance or tachyphylaxis. At the cellular level, a variety of changes are observed following repeated or continuous exposure of neurons to certain neurotransmitters. These changes include desensitization, internalization and resensitization. These cellular processes may also be involved in the development of dependence to drugs and in the development of side effects to certain drugs. The overall goal of this proposal is to examine the molecular mechanisms involved in desensitization internalization and resensitization of receptors for substance P and gonadotrophin-releasing hormone in single neurons isolated from sympathetic ganglia. Sympathetic neurons have receptors for both of these peptides an respond to the peptides with changes in cell membrane conductance. By monitoring this conductance, the cellular state with regard to desensitization, internalization and resensitization can be assessed. The techniques used to study single cells permit the precise control of intracellular and extracellular solutions. These techniques will permit the cellular changes in response to neurotransmitters to be studied in single cells with precision that has not been previously achieved. The major questions to be addressed in these studies are: 1) What are the molecular mechanisms involved in the internalization of the substance P receptor in single neurons? 2) What are the requirements for resensitization of the substance P receptor? 3) What is the mechanism for desensitization of responses to gonadotrophin-releasing hormone?

描述神经系统的运作是通过传导来自一个人的脉冲来进行的。 神经元通过突触传递传递到另一个神经元。 重要事件 突触传递是神经递质从突触前 神经元和神经递质与受体蛋白的结合， 突触后细胞的膜。 这种突触传递的过程 是神经系统运作的基础 除了 内源性神经递质，许多外源性化合物，包括 治疗剂和非治疗剂，与神经递质受体结合 从而改变神经元功能。 在许多情况下，反复或持续接触毒品或 神经递质导致神经元对 药物或神经递质 这种变化往往涉及减少 对这种药物的敏感性。 在治疗剂的情况下，这可以被观察为 耐受性或快速耐受性的发展。 在细胞层面， 在重复或连续暴露于 神经元对某些神经递质的反应 这些变化包括 脱敏、内化和再敏化。 这些细胞 这些过程也可能参与药物依赖的发展， 某些药物的副作用 本提案的总体目标是研究分子机制 参与受体的脱敏、内化和再敏化 P物质和促性腺激素释放激素在单个神经元 从交感神经节分离出来的 交感神经元有受体， 这两种肽都对细胞中的变化的肽作出反应， 膜电导 通过监测这种传导， 关于脱敏，内化和再敏化可以是 评估。 用于研究单细胞的技术允许精确的 控制细胞内和细胞外溶液。 这些技术将 允许研究响应神经递质的细胞变化 在单个细胞中的精确度是以前没有达到的。 在这些研究中要解决的主要问题是：1）什么是 P物质内化的分子机制 单个神经元中的受体 2)有什么要求 P物质受体的再敏感化 3)机制是什么 对促性腺激素释放激素反应的脱敏