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.

在本研究中，我们试图从生化和药理学的角度阐明纹状体多胺受体的功能机制，并讨论多巴胺能神经元活动的调节机制。结果，获得了以下结果。通过按照Berridge方法使用大鼠纹状体进行切片实验，检查了混合多巴胺剂如多胺或阿朴吗啡刺激的磷脂酰肌醇转换。结果，观察到 PI、P2、P3 的增加，并且这些增加是剂量依赖性的。使用 SCH 23390 或螺哌隆的抑制实验表明，PI 转变的这种加速依赖于多胺 D2 受体。腹腔注射CCK 8类似物，观察CCK对大鼠层间多巴胺释放的影响。为此，进行了体内微透析实验，结果增加了 CCK 对多胺释放的影响。另外，从即早期基因的角度研究了神经肽和多巴胺之间的关系。注意到戊四唑引起的c-fos激活被CCK和神经激肽抑制，并且这种抑制被多胺拮抗。此外，我们证实这些神经肽抑制大鼠层中酪氨酸羟化酶的基因表达。需要强调的是，多巴胺和神经肽的信号转导之间存在两种串扰，即基因组串扰和非基因组串扰。