MECHANISMS OF SYNAPTIC MODULATION IN SYMPATHETIC NEURONS

交感神经元突触调节机制

• 批准号: 2265766
• 负责人: MARK A. SIMMONS
• 金额: $ 6.89万
• 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 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265766
• 关键词: Rana; alternatives to animals in research; biological signal transduction; diacylglycerols; flash photolysis; hydrolysis; inositol phosphates; intracellular; membrane potentials; molecular cloning; neurons; neurotransmitter receptor; peptides; phosphatidylinositols; phosphorylation; potassium channel; protein structure function; receptor sensitivity; substance P; sympathetic ganglion; synapses

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 this neurotransmitter to receptors on the membrane of a postsynaptic cell. Binding of a neurotransmitter to a receptor eventually leads to a change in the ionic conductance of the postsynaptic cell. The biochemical processes that lead from membrane receptors to changes in ionic conductances are called signal transduction pathways. Many of the details of these signal transduction processes are not well understood, even though these processes underlie nervous system function in both normal and disease states. There are two major problems that will be investigated in this proposal: (1) the intracellular biochemical mechanisms involved in the transduction of neurotransmitter signals between membrane receptors and ionic channels and (2) the relationship between the molecular structure of the membrane receptors for neurotransmitters and their functions. The techniques to be applied in the proposed studies will provide precise control of intracellular and extracellular solutions, as well as of membrane potential. With accurate control over experimental conditions, it should be possible to study the signal transduction pathways with precision that has not been applied to these problems previously. Sympathetic neurons will serve as the model system to study the molecular mechanisms involved in signal transduction between membrane receptors and ion channels. The sympathetic ganglia provide a valuable preparation for the analysis of the actions of drugs and neurotransmitters. Studies of sympathetic neurons have provided considerable insight into the mechanisms of similar synaptic events that occur in the brain and spinal cord. Signal transduction pathways similar to the ones to be studied here are found throughout the nervous system and in cardiac and smooth muscle. This proposal will examine how intracellular application of various portions of the substance P receptor affects the response to substance P. Biochemical studies indicate that receptor desensitization may involve phosphorylation of the carboxyl tail of the receptor, but supporting evidence for a role of the receptor molecule in desensitization in intact neurons is lacking. Furthermore, the portions of the receptor involved in desensitization are not known. To determine which parts of the membrane receptors mediate various functions of the receptor, peptide fragments of small portions of the receptor will be applied intracellularly.

神经系统通过将脉冲从一个神经元传导到 另一种是通过突触传递。 突触中的基本事件 传递是神经递质从突触前 神经元和这种神经递质与受体的结合， 突触后细胞的膜。 一种神经递质与 受体最终导致的离子电导的变化， 突触后细胞 从细胞膜开始的生化过程 感受离子电导变化的受体称为信号传导 途径。 这些信号转导过程的许多细节是 尽管这些过程是神经系统的基础， 在正常和疾病状态下都能发挥作用。 这份提案将调查两大问题： (1)参与转导的细胞内生化机制 膜受体和离子通道之间的神经递质信号 以及（2）膜的分子结构之间的关系 神经递质受体及其功能。 使用方法以 在拟议的研究中应用将提供精确的控制， 细胞内和细胞外溶液，以及膜 潜力 通过对实验条件的精确控制， 可以精确地研究信号转导途径， 以前没有应用于这些问题。 交感神经元将作为模型系统来研究分子 参与膜受体之间信号转导的机制， 离子通道 交感神经节为 药物和神经递质作用的分析。 研究 交感神经元提供了相当多的见解， 发生在大脑和脊髓中的类似突触事件的机制 线. 与待研究的信号转导途径相似的信号转导途径 这里发现整个神经系统和心脏和平滑 肌肉. 该建议将研究细胞内应用各种 P物质受体的一部分影响对P物质的反应。 生化研究表明受体脱敏可能涉及 磷酸化的羧基尾的受体，但支持 证据表明受体分子在未受损细胞的脱敏中起作用， 神经元缺乏。 此外，受体参与的部分 在脱敏中是未知的。 为了确定 膜受体介导受体、肽 受体的一小部分片段将被应用于 细胞内。