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Cellular mechanism of long-term modulatory synaptic changes (1989)

长期调节突触变化的细胞机制 (1989)

基本信息

批准号：
62570064
负责人：
KOBAYASHI Haruo
金额：
$ 1.22万
依托单位：
Tokyo Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

Superior cervical ganglia (SCG) of rabbits were mainly used in this research project.1) Slow muscarinic depolarizing postsynaptic potentials were durably enhanced following brief exposure of the ganglion to dopamine. Similar long-term enhancement (LTE) was also produced by a treatment with cyclic AMP. Antagonists of D_1-dopaminergic receptors blocked both of the production of LTE and cAMP synthesis. These suggest that activation of D_1-receptors causes in sympathetic neurons an elevation of cAMP which in turn produces some enduring neuronal change that underlies an amplification of the muscarinic depolarizing synoptic response.2) Cyclic GMP-dependent protein kinase (G-kinase) activity was detected in SCG and two endogenous substrate proteins (90K and 54K) were identified. Phosphorylation of these proteins were increased following activation of M_1-muscarinic receptors. It is likely that cGMP-dependent protein phosphorylation system may be involved as an intracellular signal transduction process for the generation of slow muscarinic depolarizing synoptic response.3) Activation of M_2-muscarinic receptors caused a depression of Ca^<2+> influx during action potentials. This muscarinic effect appeared to be mediated by phosphatidylinositol breakdown and subsequent activation of C-kinase system.4) Various muscarinic trans-synaptic events have been shown in this study to be coupled to the different intracellular transduction systems and operated different neuronal functions.

本研究主要采用家兔颈上神经节（SCG）为研究对象。1）多巴胺短暂刺激SCG，可使慢毒蕈碱去极化突触后电位持续增强。环磷酸腺苷治疗也产生了类似的长期增强（LTE）。多巴胺D_1受体拮抗剂可阻断LTE的产生和cAMP的合成。这些结果表明，D_1受体的激活可引起交感神经元cAMP的升高，进而引起神经元的某些持久性变化，这种变化是毒蕈碱去极化综合反应放大的基础。2）在SCG中检测到环GMP依赖的蛋白激酶（G-kinase）活性，并鉴定出两种内源性底物蛋白（90 K和54 K）。M_1受体激活后，这些蛋白质的磷酸化程度增加。推测cGMP依赖的蛋白磷酸化系统可能参与了慢去极化的细胞内信号转导过程。3）激活M_2受体可抑制动作电位过程中的Ca^2+内流。这种毒蕈碱效应似乎是通过磷脂酰肌醇的分解和随后的C-激酶系统的激活来介导的。4）在本研究中已经显示了各种毒蕈碱跨突触事件与不同的细胞内转导系统偶联并且操作不同的神经元功能。