NEUROPEPTIDE BIOSYNTHESIS AND METABOLISM IN THE CNS

中枢神经系统中的神经肽生物合成和代谢

• 批准号: 3381091
• 负责人: JEFFREY D WHITE
• 金额: $ 8.81万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3381091
• 关键词: carboxypeptidase; caudate nucleus; endopeptidases; enkephalins; high performance liquid chromatography; hippocampus; laboratory rat; lenticular nucleus; messenger RNA; neuropeptides; neurotransmitter biosynthesis; neurotransmitter metabolism; putamen

Neuropeptides are now recognized to be an integral part of chemical neurotransmission in the central nervous system; however, little is known regarding the regulation of the metabolism of this class of transmitters. The proposed research is directed toward defining the dynamics of the intracellular metabolism of the opiate peptide enkephalin in specific projection systems within the rat central nervous system. Several aspects of enkephalin metabolism will be studied using both in vivo and in vitro techniques: (a) the rate of enkephalin utilization in the projection from the caudate-putamen to the globus pallidus and in the mossy fiber system of hippocampal granule cells will be determined in both control and physiologically or pharmacologically stimulated animals. These data will be combined with an analysis of the induced changes in preproenkephalin mRNA and in enkephalin content to arrive at an overall understanding of the regulation of enkephalin biosynthesis. For these studies in vivo pulse labeling of cell bodies with radioisotopic amino acid will be followed by the purification of radiolabeled Met-enkephalin containing peptides from terminal fields using sequential high performance liquid chromatography. (b) Using the same in vivo labeling techniques, the specific activity of the peptides present in the readily releaseable pool will be determined in both control and stimulated animals. (c) The activity of the enzymes responsible for the post-translational liberation of Met-enkephalin from proenkephalin will be studied in secretory granules purified from the striatum and from the hippocampus from both control and stimulated animals. The information obtained from these experiments will be essential in interpreting the potential physiological roles for the enkephalin peptides in these two projection systems and can serve as a basis for examining the metabolism of other CNS neuropeptides.

神经肽现在被认为是化学物质的组成部分， 中枢神经系统中的神经传递;然而， 关于调节这类递质的代谢。 所提出的研究是针对定义的动态 阿片肽脑啡肽的细胞内代谢 大鼠中枢神经系统内的投射系统。 几个方面 脑啡肽代谢的研究将使用在体内和体外 技术：（a）脑啡肽的利用率， 尾壳核到苍白球和 海马颗粒细胞将在对照和 生理或刺激的动物。 这些数据将 并结合对前脑啡肽原的诱导变化进行分析 mRNA和脑啡肽含量，以达到对脑啡肽的整体了解。 脑啡肽生物合成的调节。 对于这些研究，体内脉冲 用放射性同位素氨基酸标记细胞体后， 纯化放射性标记的含甲硫氨酸脑啡肽， 终端领域使用连续高效液相色谱法。 (b)使用相同的体内标记技术， 将测定易释放池中存在的肽， 对照组和受刺激组的动物。 (c)的酶的活性 负责翻译后释放甲硫氨酸脑啡肽从 脑啡肽原将研究从分泌颗粒纯化， 纹状体和海马的神经元 动物 从这些实验中获得的信息将是必不可少的 在解释脑啡肽的潜在生理作用时， 肽在这两个投影系统，并可以作为基础， 检查其他CNS神经肽的代谢。