MECHANISMS OF SYNAPTIC MODULATION IN SYMPATHETIC NEURONS

交感神经元突触调节机制

• 批准号: 6358314
• 负责人: MARK A. SIMMONS
• 金额: $ 13.98万
• 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 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6358314
• 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?

描述神经系统通过传导来自一个人的冲动而运作。 神经元通过突触传递到另一个神经元。《华尔街日报》的重要事件 突触传递是指从突触前释放的神经递质 神经元及其受体蛋白与神经递质的结合 突触后细胞膜。这种突触传递的过程是 神经系统功能的基础。除了……之外 内源性神经递质，许多外源性化合物，包括 与神经递质受体结合的治疗和非治疗药物 从而改变神经功能。 在许多情况下，反复或持续接触药物或 神经递质导致神经元对 这种药物或神经递质。通常，这种变化涉及到减少 对这种药物的敏感性。对于治疗剂，这可能被观察到为 耐受性或快速性的发展。在细胞层面上，一个 反复或连续暴露后，观察到各种变化 神经元对某些神经递质的影响。这些变化包括 脱敏、内化和复敏。这些细胞 过程也可能参与药物依赖的形成和发展。 在某些药物的副作用发展中。 这项提议的总体目标是研究分子机制。 参与受体的脱敏、内化和再增敏 P物质和促性腺激素释放激素在单个神经元中的表达 从交感神经节分离出来。交感神经元有受体 这两种多肽都能对细胞发生变化的多肽产生反应 膜电导。通过监测这种电导，细胞状态 关于脱敏，内化和再敏化可以是 评估过了。用来研究单个细胞的技术允许精确的 控制细胞内和细胞外的溶液。这些技术将 允许研究细胞对神经递质的反应变化 在单个电池中，具有以前从未达到的精确度。 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)对 P物质受体的再增敏？3)其作用机制是什么 促性腺激素释放激素反应的脱敏？

项目成果

Desensitization of the inhibition of the M-current in sympathetic neurons: effects of ATP analogs, polyanions, and multiple agonist applications.

交感神经元 M 电流抑制的脱敏：ATP 类似物、聚阴离子和多种激动剂应用的影响。

• DOI: 10.1016/0896-6273(90)90113-t
• 发表时间: 1990
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Simmons,MA;Becker,JB;Mather,RJ
• 通讯作者: Mather,RJ

Solution structures in SDS micelles and functional activity at the bullfrog substance P receptor of ranatachykinin peptides.

• DOI: 10.1021/jm000093v
• 发表时间: 2000-04
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: S. Perrine;T. Whitehead;R. Hicks;J. Szarek;J. Krause;M. A. Simmons

Neurokinin-1 receptor resensitization precedes receptor recycling.

Neurokinin-1 受体再敏化先于受体再循环。

• DOI: 10.1124/jpet.104.079954
• 发表时间: 2005
• 期刊: The Journal of pharmacology and experimental therapeutics.
• 作者: Bennett,VJ;Perrine,SA;Simmons,MA
• 通讯作者: Simmons,MA

Regulation of M-type potassium current by intracellular nucleotide phosphates.

细胞内磷酸核苷酸对 M 型钾电流的调节。

• DOI: 10.1523/jneurosci.18-16-06254.1998
• 发表时间: 1998
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Simmons,MA;Schneider,CR
• 通讯作者: Schneider,CR

Molecular characterization and functional expression of a substance P receptor from the sympathetic ganglion of Rana catesbeiana.

林蛙交感神经节 P 物质受体的分子特征和功能表达。

• DOI: 10.1016/s0306-4522(97)00027-4
• 发表时间: 1997
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Simmons,MA;Brodbeck,RM;Karpitskiy,VV;Schneider,CR;Neff,DP;Krause,JE
• 通讯作者: Krause,JE