Control of the adenylate cyclase system by GABA_b receptors

GABA_b 受体对腺苷酸环化酶系统的控制

• 批准号: 60580143
• 负责人: ASANO Tomiko
• 金额: $ 0.83万
• 依托单位: Institute for Developmental Research,Aichi Prefectural Colony
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60580143/
• 关键词: GABA_b receptors; GTP-binding protein; calmodulin; immunoallay; 免疫組織化学; カルモジュリン

To make clear the mechanism of presynaptic inhibition,the signal transduction mediated by GABA_b reseptors was investigated. The findings in this research project are as follows.1. GABA_b reseptors are coupled to pertussis toxin-sensitive GTP-binding proteins,G_i and G_o, in the brain membranes.2. N-Ethylmaleimide uncouples GABA_b reseptors from GTP-binding proteins by the similar mechanism of pertussis toxin.3. G_i and G_o inhibited calmodulin-stimulated cyclic nucleotide phosphodiesterase. GTP-binding proteins seem to bind directly to calmodulin in a Ca^<2+>-dependent manner.4. Highly sensitive immunoassay method for the quantification of the <alpha> subunit of G_o (G_o<alpha>) was developed. The tissue and cellular distridution of G_o<alpha> was investigated in the rat. The results indicate that G_o is localized exclusively in the nervous tissues and neuroendocrine cells.5. Immunoassya method for the quantification of the <beta> subunit of GTP-binding proreins was also developed. The concentrations of <beta> subunit were higher than those of G_o<alpha> in the brain.

为了明确突触前抑制的机制，我们研究了GABA_b受体介导的信号转导。本研究项目的研究结果如下：1。GABA_b受体在脑膜中与百日咳毒素敏感的gtp结合蛋白G_i和G_o偶联。n -乙基马来酰亚胺通过类似百日咳毒素的机制将GABA_b受体从gtp结合蛋白上解耦。G_i和G_o抑制钙调素刺激的环核苷酸磷酸二酯酶。gtp结合蛋白似乎以Ca^<2+>依赖的方式直接与钙调蛋白结合。建立了高灵敏度的定量G_o< α >亚基（G_o< α >）的免疫分析方法。研究了大鼠组织和细胞中G_o< α >的分布。结果表明，G_o只存在于神经组织和神经内分泌细胞中。此外，还建立了定量测定gtp结合蛋白< β >亚基的免疫分析方法。脑内< β >亚基浓度高于G_o< α >亚基浓度。

项目成果

Tomiko Asano: "Interaction of GTP-binding proteins with calmodulin" FEBS Letters. 203. 135-138 (1986)

Tomiko Asano：“GTP 结合蛋白与钙调蛋白的相互作用”FEBS Letters。

Kanefusa Kato: "Production of the <alpha> subunit of guanine nucleotide-binding protein G_o by neuroendocrine tumors" Cancer Research. 47. 5800-5805 (1987)

Kanefusa Kato：“神经内分泌肿瘤产生鸟嘌呤核苷酸结合蛋白 G_o 的 <α> 亚基”癌症研究。

Tomiko Asano: "Highly sensitive immunoassay for the <alpha> subunit of the GTP-binding protein G_o and its regional distribution in bovine brain" Journal of Neurochemistry. 48. 1617-1623 (1987)

Tomiko Asano：“GTP 结合蛋白 G_o 的 <α> 亚基及其在牛脑中的区域分布的高灵敏度免疫测定”《神经化学杂志》。

Tomiko Asano: FEBS Letters. 203. 135-138 (1986)

浅野富子：FEBS 信件。

Tomiko Asano: Journal of Neurochemistry. (1987)

浅野富子：神经化学杂志。