Control of the adenylate cyclase system by GABA_b receptors

为了阐明突触前抑制的机制，我们对GABA_（B）受体介导的信号转导进行了研究。本研究的主要结果如下：1. GABA_B受体与脑细胞膜上百日咳毒素敏感的GTP结合蛋白G_i和G_o偶联. N-乙基马来酰亚胺通过与百日咳毒素类似的机制将GABA_B受体从GTP结合蛋白上解偶联. 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素结合.建立了一种高灵敏度的<alpha>G_o亚基（G_o<alpha>）免疫分析方法。本文观察了大鼠G_o的组织和细胞分布<alpha>。结果表明，G_o只定位于神经组织和神经内分泌细胞.还<beta>建立了定量测定GTP结合蛋白亚基的免疫分析方法。脑<beta>内亚基含量高于G_o<alpha>。

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.