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离体兔肾近端小管中细胞外ATP引起细胞内钙离子浓度升高的机制

Mechanism of [Ca2+]i increase by extracellular ATP in isolated rabbit renal proximal tubules.

作者信息

Yamada H, Seki G, Taniguchi S, Uwatoko S, Suzuki K, Kurokawa K

机构信息

First Department of Internal Medicine, Tokyo University School of Medicine, Japan.

出版信息

Am J Physiol. 1996 Apr;270(4 Pt 1):C1096-104. doi: 10.1152/ajpcell.1996.270.4.C1096.

DOI:10.1152/ajpcell.1996.270.4.C1096
PMID:8928737
Abstract

The effects of extracellular ATP on cytosolic Ca2+ concentrations ([Ca2+]i) and cell membrane potentials (Vb) of rabbit renal proximal tubules were investigated using fura 2 and microelectrodes. ATP transiently increased [Ca2+]i without an apparent sustained phase, and the maximum effect was obtained at 10 microM. ADP, adenosine 5'-O-(3-thiotriphosphate), and 2-methylthioadenosine 5'-triphosphate were equally effective as ATP, whereas UTP, adenosine, and alpha beta-methyleneadenosine 5'-triphosphate were far less effective. The [Ca2+]i responses to ATP were strongly inhibited by reactive blue 2, a P2-purinergic receptor antagonist. The removal of extracellular Ca2+ as well as the addition of thapsigargin also markedly attenuated the responses to ATP. In addition, ATP had virtually no effect on Vb, except for the occasional small depolarization by 300 microM ATP. These results indicate that extracellular ATP increases [Ca2+]i through a P2-purinergic receptor and that this effect of ATP is dependent on both extracellular and intracellular Ca2+.

摘要

利用fura 2和微电极研究了细胞外ATP对兔肾近端小管细胞溶质Ca2+浓度([Ca2+]i)和细胞膜电位(Vb)的影响。ATP可使[Ca2+]i短暂升高,无明显的持续阶段,在10微摩尔时可获得最大效应。ADP、腺苷5'-O-(3-硫代三磷酸)和2-甲硫基腺苷5'-三磷酸与ATP具有同等效力,而UTP、腺苷和αβ-亚甲基腺苷5'-三磷酸的效力则远低于ATP。对ATP的[Ca2+]i反应受到P2-嘌呤能受体拮抗剂活性蓝2的强烈抑制。去除细胞外Ca2+以及添加毒胡萝卜素也显著减弱了对ATP的反应。此外,除了300微摩尔ATP偶尔引起的小去极化外,ATP对Vb几乎没有影响。这些结果表明,细胞外ATP通过P2-嘌呤能受体增加[Ca2+]i,且ATP的这种作用依赖于细胞外和细胞内的Ca2+。

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