Antidromic nerve regulation and effecter protection by ATP released from effector cell

效应细胞释放的 ATP 的逆向神经调节和效应保护

• 批准号: 14570094
• 负责人: SHINZOUKA Kazumasa
• 金额: $ 2.11万
• 依托单位: Mukogawa Women's University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570094/
• 关键词: ATP; rat caudal artery; permeability; noradrenaline; cultured endothelial cell; symapthetic nerves; cell shape regulation; ATP遊離; 自律神経; 神経伝達; 低温; 低酸素; 低浸透圧; プリン受容体; シナプス前調節

The protective role of antidromic regulation of neurptransmission by ATP was examined.(1)The distribution of mechanism of ATP release :In the 11 kinds of tissue preparations, electrical stimulation(ES) at 10Hz elicited the release of ATP. In the caudal artery, the amount of ATP-release was the most.(2)ATP release by nerve stimulation.The releases of noradrenaline(NA) and purine compounds by ES were increased in frequency-dependent manner. In addition, the release of purine compounds was increased in the NA concentration dependent manner. Therefore, it was suggested that release of a purine compounds depends on the excitation of the nervous system.(3)Protective effect by release ATP : Inhibitory action on NA-release :ES at high frequency, ATP and alpha-adrenoceptor agonist at higher concentration produced release of purine compound, and the endogenous purines inhibit the release of NA from sympathetic nerves.(4)Protective effect by release ATP : promotion of permeability :We observed th … More at the permeability of the vascular endothelium cell layer was promoted by purinergic receptor agonist, by the experiment using culture endothelial cells of rat caudal artery. This permeable promotion was also observed in rat caudal artery preparation.(5)Relation with disease : Dysfunction of antidromic regulation in life-style-related diseases of rat.Purinergic receptor on the sympathetic nerve ending did not function in genetic life-style related diseases rat(SHR/NDmcrcp). The release of endogenous purines was not changed in the disease model rat.These results suggested the following hypothesis ; When the arterial sympathetic nerve was excited extremely, an endogenous purines were released and inhibited neurotransmission and then improved bloodstream, and furthermore enhanced in permeability of endothelial cell layer and improved material transport to peripheral tissues. So, ATP seems to protect peripheral effector tissues through these two pathways, and may be important factor on the onset and development of life-style related diseases. Less

研究了ATP对神经传递的反序调节的保护作用。(1) ATP释放机制分布：在11种组织制剂中，10Hz电刺激（ES）可诱导ATP释放。尾动脉中atp释放量最大。(2)神经刺激释放ATP。ES释放的去甲肾上腺素（NA）和嘌呤类化合物呈频率依赖性增加。此外，嘌呤类化合物的释放呈NA浓度依赖性增加。因此，有人认为嘌呤化合物的释放依赖于神经系统的兴奋。(3)释放ATP的保护作用：对NA释放的抑制作用：ES高频时，ATP和α -肾上腺素受体激动剂高浓度时产生嘌呤化合物的释放，内源性嘌呤抑制交感神经NA的释放。(4)释放ATP的保护作用：促进血管通透性：通过培养的大鼠尾动脉内皮细胞实验，我们观察到嘌呤能受体激动剂对血管内皮细胞层通透性的促进作用。在大鼠尾动脉制备中也观察到这种促进渗透的作用。(5)与疾病的关系：大鼠生活方式相关疾病的反节律调节功能障碍。交感神经末梢嘌呤能受体在遗传性生活方式相关疾病大鼠（SHR/ ndmccp）中不起作用。内源性嘌呤的释放在疾病模型大鼠中没有改变。这些结果提出了以下假设：当动脉交感神经极度兴奋时，内源性嘌呤释放抑制神经传递，改善血流，进而增强内皮细胞层的通透性，促进物质向外周组织的转运。因此，ATP似乎通过这两种途径保护外周效应组织，并可能是生活方式相关疾病发生发展的重要因素。少

项目成果

Shinozuka K. et al.: "Purinergic modulation of vascular symoathetic neurotransmission."Jananese Journal of Pharmacology. 88. 19-25 (2002)

Shinozuka K.等人：“血管交感神经传递的嘌呤能调节。”Jananese Journal of Pharmacology。

橋本道男, 田中直子, 藤井由已, 窪田洋子, 篠塚和正, 国友 勝、紫藤 治: "ニコランジルによる血管内皮細胞からのATP遊離促準作用にミトコンドリアATP感受性K^+チャネルは関与するか?"Therapeutic Research. 24. 0-15 (2003)

Michio Hashimoto、Naoko Tanaka、Yoshimi Fujii、Yoko Kubota、Kazumasa Shinozuka、Masaru Kunitomo、Osamu Shito：“线粒体 ATP 敏感 K^+ 通道是否参与尼可地尔促进血管内皮细胞释放 ATP？” 24 0-15 (2003)

Shinozuka K. et al.: "Purinergic modulation of vascular sympathetic neurotransmission."Japanese Journal of Pharmacology. 88. 19-25 (2002)

Shinozuka K.等人：“血管交感神经传递的嘌呤能调节。”日本药理学杂志。

Tanaka N. et al.: "P2Y-receptor regulates size of endothelial cells in an intracellular Ca(2+) dependent manner"Life Science. 72. 1445-1453 (2003)

Tanaka N. 等人：“P2Y 受体以细胞内 Ca(2) 依赖性方式调节内皮细胞的大小”生命科学。

Tanaka N. et al.: "P2Y receptor-mediated enhancement of permeation requires Ca^<2+> signalling in vascular endothelial cells"Clinical and Experimental Pharmacology and Physiology. 30. 649-652 (2003)

Tanaka N.等人：“P2Y受体介导的渗透增强需要血管内皮细胞中的Ca 2+ 信号传导”临床和实验药理学和生理学。