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Establishment of the pharmacological sciences to elucidate the signal transduction system.

建立药理学科学来阐明信号转导系统。

基本信息

批准号：
04304030
负责人：
HIDAKA Hiroyoshi
金额：
$ 9.6万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

One of the aims of this research project was to elucidate and control the mechanisms by which the intracellular second messenger systems transduce signals derived from extracellular stimuli, using specific molecular probes. The other was to create novel function-targeted probes which are useful to investigate the intracellular mechanisms. Such a pharmacological approach is undoubtedly powerful since various biological phenomena are controlled by a network of multiple intracellular messenger systems. Through three-year work under this grant, increasing number of specific molecular probes have became available, which enabled us to understand intracellular messenger systems. A good example is KN-62 and 93, specific inhibitors of Ca/calmodulin-dependent protein kinase II,which have been widely used to investigate the functions of the kinase. We also succeeded to purify the novel type of Ca/calmodulin-dependentkinase. V.We obtained evidence concerning signal transduction mechanisms by tachykinin, GABA and serotonin in neurons using pharmacological agents. Nitric oxide was demonstrated to be involved in the neural control of the brain vessel dilation.From an molecular biological approach, two types of Ca channels releasing Ca^<2+>from the intracellular store sites have been cloned. All these findings indicate that novel specific probes are desperately required for fundamental understanding of the intracellular messenger systems. Furthermore, these probes may provide a clue to create new compounds for a clinical use.

本研究项目的目的之一是阐明和控制的机制，细胞内的第二信使系统的信号来自细胞外刺激，使用特定的分子探针。另一个是建立新型的功能靶向探针，用于研究细胞内机制。这种药理学方法无疑是强大的，因为各种生物现象是由多个细胞内信使系统的网络控制的。通过三年的工作，越来越多的特定分子探针已经成为可用的，这使我们能够了解细胞内的信使系统。一个很好的例子是KN-62和93，它们是Ca/钙调素依赖性蛋白激酶II的特异性抑制剂，已被广泛用于研究激酶的功能。我们还成功地纯化了新型的Ca/钙调素依赖性激酶。我们通过药理学手段获得了有关速激肽、GABA和5-羟色胺在神经元中的信号转导机制的证据。一氧化氮（NO）参与了脑血管扩张的神经调控，从分子生物学的角度，克隆了两种从细胞内钙库释放Ca^2+的钙通道。所有这些发现表明，新的特异性探针是迫切需要的细胞内信使系统的基本理解。此外，这些探针可能为创造用于临床的新化合物提供线索。