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Molecular biologocal studies on the regulation of neuropeptide synthesis by dopamine

多巴胺调节神经肽合成的分子生物学研究

基本信息

批准号：
61480118
负责人：
TNAKA Chikako
金额：
$ 4.16万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

Regulation of the neuropeptide synthesis by dopamine is thought to be initiated by the stimulation of the receptor,and as a result of various intracellular biochemical events,the change in the translation rate of the neuropeptide gene is observed. Althogh details of these mechanisms are unknown, second messenger systems such as cyclic nucleotides and phosphatidylinositol turnover have been reported to be involved in the regulation. In the present study, following results were obtained on the molecular structures and tissue distributions of several protein kinases which seem to play important roles in the these second messenger systems.1. We obtained the cDNA clone which contains the entire coding regoin of the type I regulatory subnit of syclic AMP-dependent protein kinase from a rat brain cDNA library by a homology proding method based on the amino acid sequence was deduced by the nucleotide sequence of the cDNA clone. Molecular weight of the subunit was determined by the homology with other cyclic nucleotide binding proteins.2. The presence of various subtypes of protein kinase C has been shown by molecular cloning techniques. Gamma<gamma>subtype of the protein kinase C mainly localizans in the central nervous system, and Purkinje cells in the cerebellum and pyramidal cells in the hippocampus showed strong immunoreactivities. Furthermore, <beta>_1 and <beta>_2 subtypes which are produced by alternative splicing mechanism also showed specific distinct localization in the neurons and nerve terminals. These results indicate that different subtypes of protein kinase C may be crrelated with different neuronal functions.

多巴胺对神经肽合成的调节被认为是由受体的刺激启动的，并且由于各种细胞内生化事件，观察到神经肽基因翻译率的变化。虽然这些机制的细节尚不清楚，但据报道，第二信使系统如环核苷酸和磷脂酰肌醇转换参与了调节。在本研究中，我们对在这些第二信使系统中起重要作用的几种蛋白激酶的分子结构和组织分布进行了如下研究。利用同源性诱导的方法，从大鼠脑cDNA文库中获得了包含syclic amp依赖性蛋白激酶I型调控亚基全部编码区蛋白的cDNA克隆，并根据该cDNA克隆的核苷酸序列推断其氨基酸序列。通过与其他环核苷酸结合蛋白的同源性来确定该亚基的分子量。通过分子克隆技术已证实存在多种蛋白激酶C亚型。蛋白激酶C的γ < γ >亚型主要分布于中枢神经系统，小脑浦肯野细胞和海马锥体细胞表现出较强的免疫反应性。此外，通过选择性剪接机制产生的< β >_1和< β >_2亚型在神经元和神经末梢也表现出特定的不同定位。这些结果提示不同亚型的蛋白激酶C可能与不同的神经元功能相关。