DELTA OPIOIDS REGULATE NEURONAL DIFFERENTIATION

Delta 阿片类药物调节神经元分化

• 批准号: 2614618
• 负责人: MANOLIS MERKOURIS
• 金额: $ 2.86万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2614618
• 关键词: biological signal transduction; cell differentiation; cell line; cytoskeleton; gene expression; immunocytochemistry; neurogenesis; neurons; opioid receptor; protein kinase; tissue /cell culture; transfection

Opioid peptides regulate neuronal shape and function. I will test the hypothesis that the role of the opioid receptor the cortical cytoskeleton, neuronal shape, and neuronal function, i.e., neuro- transmitter secretion. Neuronal shape and function are tightly interrelated events. An integral and important part of this molecular interaction circuit is the membrane receptor, which stimulates specific signaling pathways to mediate information from the microenvironment. This chain of molecular interactions leads to normal neuronal function. The specific aims are to express and overexpress the mouse delta-opioid receptor in PC12 and NG108x15 cell lines and (a) establish the regulation of neuronal shape by showing that the delta-opioid receptor regulates neuritic process outgrowth; (b) determine the involvement of kinases Src, FAK in the signal transduction pathway of the delta-opioid receptor; (c) study the mechanism of regulation of the cortical cytoskeleton (posttranslational modifications of vinculin and cortactin). For the proposed studies I will use a combination of tissue culture, biochemical, immunocytochemical, and gene transfer techniques. My goal is to provide a better understanding of how the opioid receptors regulate neural function, and thus set the stage for better therapeutic interventions with opiates.

阿片类肽调节神经元的形状和功能。 我将测试 假说阿片受体的作用是皮质的 细胞骨架，神经元形状和神经元功能，即神经 - 发射器分泌。 神经元的形状和功能是紧密相互关联的事件。 一个 该分子相互作用回路的积分和重要部分是 膜受体，刺激特定的信号通路 从微环境中调解信息。 这条分子链 相互作用导致正常的神经元功能。 具体目的是 在PC12和 NG108x15细胞系和（a）建立神经元形状的调节 通过表明三角洲阿片受体调节神经过程 出生（b）确定激酶SRC的参与，FAK 三角洲阿片受体的信号转导途径； （c）研究 皮质细胞骨架调节的机理（翻译后 Vinculin和Cortactin的修饰）。 对于拟议的研究 将结合组织培养，生化， 免疫细胞化学和基因转移技术。 我的目标是提供 更好地了解阿片受体如何调节神经 功能，因此为更好的治疗干预奠定了基础 与阿片类药物。