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Identification of P2-purinergic receptors

P2-嘌呤能受体的鉴定

基本信息

批准号：
09672208
负责人：
MURAYAMA Toshihiko
金额：
$ 1.28万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672208/
关键词：
ATP receptor PC12 cells glial cells adenylyl cyclase ARF S-nitroso-cysteine NO synthase ATP プリン受容体 GTP結合蛋白質 NO ホスホリパーゼA_2 アラキドン酸

项目摘要

1) PC12 pheochromocytoma cells have P2 receptors which are coupled to Ca2+influx and catecholamine release. In the presence of forskolin, an activator of adenylyl cyclase, ATP analogs such as ATP and 2-methylthio ATP inhibited cyclic AMP accumulation in a concentration-dependent manner. Treatment with pertussis toxin, which completely abolished the effect of carbachol, had no effect on the action of ATP.In addition, we found that ADP-ribosylation factors translocate to membranes from the cytosol fraction after exocytotic stimulation. The cloning of a new type of ATP receptor remains to be determined.2) Nitric oxide (NO) modulates the release of neurotransmitters. Previously we reported that 5-nitroso-cysteine stimulated noradrenaline release from hippocampus in vivo and in vitro. In PC12 cells, S-nitroso-cysteine did inhibit noradrenaline release. Other NO compounds, which increased cyclic GMP accumulation, had no effect. ATP-stimulated Ca2+ influx via Ca2+ channels was inhibited in PC12 cells treated with S-Nitroso-cysteine, although S-nitroso-cysteine stimulated Ca2+ mobilization from intracellular caffeine-sensitive Ca2+-pools. Ca2+ mobilization by NO from Ca2+ pools was not a sufficient factor, and other factors stimulating release may be regulated negatively.3) Lipopolysaccaride or cytokines are known to stimulate production of nitrite via expression of inducible NO synthase (iNOS) in rat glial cells. Co-addition of endothelin decreased iNOS expression and nitrite accumulation by stimulants. In contrast, pretreatment with endothelin or ATP for 24 h enhanced iNOS expression. The stimulatory effect by endothelin or ATP was mediated by ET-B or P2 receptors, respectively. A protein kinase C inhibitor suppressed endothelin- and ATP-enhanced iNOS expression. Stimulation of ATP receptors induced activation of a nuclear factor, NFkB in glial cells.

1)PC 12嗜铬细胞瘤细胞具有与Ca ~（2+）内流和儿茶酚胺释放偶联的P_2受体。在腺苷酸环化酶的激活剂forskolin存在下，ATP类似物如ATP和2-甲硫基ATP以浓度依赖性方式抑制环AMP积累。百日咳毒素治疗，完全取消卡巴胆碱的效果，有没有影响的行动ATP.In此外，我们发现，ADP-核糖基化因子转运到膜从胞质溶胶馏分后，胞吐刺激。一种新型ATP受体的克隆尚待确定。2）一氧化氮（NO）调节神经递质的释放。以前，我们报道了5-亚硝基半胱氨酸刺激去甲肾上腺素从海马在体内和体外释放。在PC 12细胞中，S-亚硝基半胱氨酸确实抑制去甲肾上腺素的释放。其他NO化合物，增加环GMP积累，没有影响。S-亚硝基半胱氨酸抑制了ATP刺激的Ca ~（2+）通道内流，但S-亚硝基半胱氨酸刺激了细胞内咖啡因敏感的Ca ~（2+）库的Ca ~（2+）动员。NO从Ca ~（2+）库中动员Ca ~（2+）并不是一个充分的因素，其他刺激Ca ~（2+）释放的因素可能是负调控的。3）脂多糖或细胞因子可以通过诱导型NO合成酶（iNOS）的表达刺激大鼠胶质细胞产生亚硝酸盐。内皮素的共同加入减少iNOS的表达和亚硝酸盐积累的兴奋剂。与此相反，用内皮素或ATP预处理24 h可增强iNOS的表达。内皮素或ATP的刺激作用分别由ET-B或P2受体介导。蛋白激酶C抑制剂抑制内皮素和ATP增强的iNOS表达。ATP受体的刺激诱导神经胶质细胞中核因子NF κ B的活化。