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ドーパミン作動性反回入力と興奮性および抑制性入力応答との細胞内クロストーク

多巴胺能循环输入与兴奋性和抑制性输入反应之间的细胞内串扰

基本信息

批准号：
07670047
负责人：
NABEKURA Junichi
金额：
$ 1.54万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

To investigate the intracellular cross-talk between the receptor for inhibitory amino acid and the monoamine receptor, the following experiments have been performed. Under the anesthesia, rats aged between 12-14 days after birth, were decapitated. The brain slices with 400 micron thickness including substantia nigra were obtained. After the treatment with enzyme, nigra neurons were acutely dissociated. The nystatin perforated patch recording were employed and the modulatory effects of monoamine on the GABA and taurine responses. The application of dopamine suppressed the GABA response. Taurine increased the membrane permeability to chloride ion by the activation of the glycine receptor-channel complex. Noradrenaline potentiated the taurine response, resulting in suppressing the neuronal excitability. The two distinct intracellular pathways were identified in the potentiation of the taurine responses by noradenaline. Activation of alpha2 adrenoceptor which is coupled to pertussis toxin-sensitive GTP binding protein suppresses adenyl cyclase activity, resulting in the decrease of intracellular cyclic AMP and protein kinase A activity. The decrease of protein kinase A activity potentiated the glycine receptor mediated taurine response.Another pathway in the modulation of taurine response by noradrenaline is as follows. Alpha2 adrenoceptor activated by noradrenaline increased the phospholipase C (PLC) activity through pertussis-toxin sensitive G protein. PLC increased the intracellular protein kinase C activity, resulting in the enhancement of glycine-receptor mediated taurine response. Single channel recording revealed that this enhancement of taurine response by alpha2 adrenoceptor activation was associated with the potentiation of the open probabillity of taurine-activated channel.These results indicate that noradrenaline enhanced the taurine response by the two distinct intracellular pathways in the rat substantia nigra neurons.

为了研究抑制性氨基酸受体和单胺受体之间的细胞内串扰，进行了以下实验。在麻醉下，将出生后12-14天的大鼠断头。获得包括黑质的400 μ m厚的脑切片。酶处理后，黑质神经元急性分离。用制霉菌素穿孔膜片记录法研究了单胺对GABA和牛磺酸反应的调制作用。多巴胺的应用抑制GABA反应。牛磺酸通过激活甘氨酸受体通道复合物增加膜对氯离子的渗透性。去甲肾上腺素增强牛磺酸反应，导致抑制神经元兴奋性。两个不同的细胞内途径被确定在增强牛磺酸的反应去甲肾上腺素。与百日咳毒素敏感性GTP结合蛋白偶联的α 2肾上腺素受体的激活抑制腺苷酸环化酶活性，导致细胞内环AMP和蛋白激酶A活性的降低。蛋白激酶A活性的降低增强了甘氨酸受体介导的牛磺酸反应。去甲肾上腺素激活的α 2肾上腺素受体通过百日咳毒素敏感的G蛋白增加磷脂酶C（PLC）活性。PLC使细胞内蛋白激酶C活性增加，从而增强甘氨酸受体介导的牛磺酸反应。单通道记录结果表明，α 2肾上腺素受体激活对牛磺酸反应的增强与牛磺酸激活通道开放概率的增强有关，提示去甲肾上腺素通过两条不同的细胞内途径增强大鼠黑质神经元对牛磺酸的反应。