Molecular biological study on modulatory effects of psychotropic agents on biosynthesis and metabolism of neuropeptides

精神药物对神经肽生物合成和代谢调节作用的分子生物学研究

基本信息

批准号：
62570140
负责人：
YOSHIKAWA Kazuaki
金额：
$ 1.47万
依托单位：
Tokyo Institute of Psychiatry
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

Various kinds of psychotropic agents exert their modulatory effects on neuronal functions through intracellular second messenger systems (e.g., protein kinases A and C). On the other hand, neuropeptides (i.e., endogenous, modulators of neuronal functions) are synthesized through the gene expression of their precursors. In this research project, we have attempted to examine modulatory roles of the second messenger systems in the gene expression of neuropeptide precursors. Major findings obtained are as follows:1) In the rat telencephalon, the preprocholecystokinin gene expression is increased at early stages of postnatal development. In addition, there is a distinct sex-related difference in the gene expression, presumably due to effect of gonadal steroid hormones.2) The expression of preproenkephalin gene in rat primary cultured cells is controlled by the activators for protein kinase A and C systems.3) Glucocorticoids (i.e., steroid hormones having neurotropic actions) potentiate,the preproenkephalin gene activation mediated by protein kinase A system, but not that mediated by protein kinase C system.4) The preproenkephalin gene is highly expressed in the rat germ cells, and the expression is hardly controlled by the protein kinase systems. The messenger RNA expressed in the germ cells shows a unique structure.Above findings indicate that the expression of preproenkephalin gene is controlled by the interactions between intracellular second messenger systems. Gene expression of other neuropeptides may be controlled by similar mechanisms, and further studies should thus be planned.

各种精神剂通过细胞内第二允许系统（例如蛋白激酶A和C）对神经元功能产生调节作用。另一方面，神经肽（即神经元功能的内源性调节剂）通过其前体的基因表达合成。在该研究项目中，我们试图检查第二质体系统在神经肽前体的基因表达中的调节作用。所获得的主要发现如下：1）在大鼠端脑中，在产后发育的早期阶段，前胆红素的基因表达增加。此外，基因表达存在明显的性别相关差异，可能是由于性腺类固醇激素的作用。2）2）蛋白激酶A和COCTORAPE A和COCTORICAITS（即，蛋白激酶A和COTYSS.3）具有神经激素的蛋白质激素的蛋白质激酶A和COTERIATION型神经蛋白酶剂量激素（即由蛋白激酶A系统介导的，而不是由蛋白激酶C系统介导的。4）preproeneenkephalin基因在大鼠生殖细胞中高度表达，并且该表达几乎不受蛋白激酶系统的控制。在生殖细胞中表达的使者RNA显示出独特的结构。放弃的发现表明，前蓝脑蛋白基因的表达受细胞内第二质体系统之间相互作用的控制。其他神经肽的基因表达可以通过相似的机制来控制，因此应计划进一步研究。