Regulatory mechanism of doaminergic signal transduction in the striatum-bichemical studies.

纹状体生化研究中多胺能信号转导的调节机制。

基本信息

批准号：
02404037
负责人：
KITO Shozo
金额：
$ 4.48万
依托单位：
THE UNIVERSITY OF THE AIR
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1993
项目状态：
已结题

项目摘要

In this studies, we tried to elucidate functional mechanism f doamine receptors in the striatum from biochemical and pharmacological viewpoints and discuss on mechanisms by which dopaminergic neuronal activtes are regulated. As results, following results were obtained.By means of slice experiments following Berridge's methds using rat striatum, phospatdyl inositol turnover stimulated by mixed dopamineagnist such as doamine or apomorphine was xamined. As results, increases of PI, P2, P3 reeases were bserved and these increases were dose-dependent.Inhibiton experiments by use of SCH 23390 or spiperone revealed that this acceeratin of PI turnver was dependent upon doamine D2 receptors.As next step, cerulein, a CCK 8 analog was ntraperitoneally injected to observe how CCK had effects on dopamine release from rat stratum. For this urpose, in vivo microdialsis experiments were done with the result of increasing effect of CCK on doamine release. In addition, relationship between neuropeptide and dopamine was studied from a viewpoint of immediate early genes. It was noticed that pentylentetrazole indused activation of c-fos was inhiited by bth CCK and neurokinin and such inhibition was antagonized by doamine. Furthermore, we confirmed that these neuropeptide inhibited gene expresion of tyrosine hydroxylase in rat stratum. Emphasis should be put on the fact that there were two hases of crosstalk, i.e. genomic and non-genomic, between sgnal transduction of dopamine and neuropeptides.

在这项研究中，我们试图从生化和药理学观点中阐明纹状体中的功能机制F doamine受体，并讨论调节多巴胺能神经元激活的机制。作为结果，获得了以下结果。通过使用大鼠纹状体，凤凰肌醇的phospatdyl肌醇转换刺激的混合多巴胺毒剂（例如doamine或apomorphine）刺激的phospatdyl肌醇周转后，通过切片实验的方式进行了切片实验。 As results, increases of PI, P2, P3 reeases were bserved and these increases were dose-dependent.Inhibiton experiments by use of SCH 23390 or spiperone revealed that this acceeratin of PI turnver was dependent upon doamine D2 receptors.As next step, cerulein, a CCK 8 analog was ntraperitoneally injected to observe how CCK had effects on dopamine从大鼠层释放。对于这种urpose，在CCK对毒胺释放的影响增加的结果上进行了体内微质体实验。此外，从直接早期基因的角度研究了神经肽和多巴胺之间的关系。人们注意到，BTH CCK和Neurokinin诱发了戊烷乙烯唑的指定激活，并且这种抑制作用被Doamine拮抗。此外，我们证实了这些神经肽在大鼠层中抑制酪氨酸羟化酶的基因的基因。应重点放在以下事实上：在多巴胺和神经肽的SGNAL转导之间存在两个串扰的大义子，即基因组和非基因组。