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Study on Physiological Roles of Neuropeptidases

神经肽酶的生理作用研究

基本信息

批准号：
01571192
负责人：
YOKOSAWA Hideyoshi
金额：
$ 1.28万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01571192/
关键词：
Neuropeptidase Neuroptetide Substance p LHRH Dynorphin Somatostatin

项目摘要

The physiological action of neuropeptides at the synape is terminated through enzymatic degradation by membrane-bound proteases. We have defined, purified, and characterized membrane-bound proteases functioning in degradation of four neuropeptides, substance P, LHRH (luteinizing hormone-releasing hormone), dynorphin, and somatostatin. 1. We have analyzed the degradation of substance P by neuronal cells cultured from rat fetal brain and found that a metallo-endopeptidase showing properties almost identical with those of the substance P-degrading enzyme purified from rat brain by us is involved in the degradation likely as the degradation by neuroblastoma cells and rat synaptic membrane. On the other hand, it was found that endopeptidase-24.11 functions in the degradation by glioma cells and glial cells cultured from rat fetal brain. The latter enzyme has been purified from glioma cells. 2. LHRH fragment (1-5)-generating enzyme that plays an important role in the initial stage of LHRH-degradation haed been purified from neuroblastoma cells and rat brain synaptic membrane. The enzyme has been characterized as a metallo-endopeptidase whose sulfhydryl groups are essential for the maintenance of the activity. It was also found that similar enzymes play important roles in degradation by neuronal and glial cells cultured from rat fetal brain. 3. One of two dynorphin-degrading cysteine proteases has been characterized as a novel enzyme with highly strict specificity toward only Arg-Argbond among four kinds of paired basic residues. 4. The degradation of somatostatin in the rat hippocampal synaptic membranes was found to be initially triggerd by the action of endopeptidase-24.11.

神经肽在突触核的生理作用通过膜结合蛋白酶的酶促降解而终止。我们已经定义，纯化，和特点的膜结合蛋白酶的功能降解的四种神经肽，P物质，LHRH（促黄体生成激素释放激素），强啡肽，和生长抑素。1.我们分析了从大鼠胎脑培养的神经细胞对P物质的降解，发现一种金属内肽酶参与了降解，其性质与我们从大鼠脑中纯化的P物质降解酶的性质几乎相同，可能与神经母细胞瘤细胞和大鼠突触膜的降解类似。另一方面，发现内肽酶-24.11在从大鼠胎脑培养的胶质瘤细胞和神经胶质细胞的降解中起作用。后一种酶已从神经胶质瘤细胞中纯化。2.从神经母细胞瘤细胞和大鼠脑突触膜中纯化了LHRH片段（1-5）生成酶，该酶在LHRH降解的初始阶段起重要作用。该酶已被表征为金属内肽酶，其巯基基团是维持活性所必需的。同时发现，类似的酶在培养的大鼠胎脑神经元和神经胶质细胞的降解中起重要作用。3.其中一种降解强啡肽的半胱氨酸蛋白酶是一种新的酶，对四种成对的碱性残基中的Arg-Arg键具有高度的特异性。4.大鼠海马突触膜生长抑素的降解最初是由内肽酶-24.11作用引起的。