Functional proteins involved in regulation of intracellular Ca2+ for drug development:: Pharmacology of SEA0400, a specific inhibitor of the Na+-Ca2+ exchanger
Functional proteins involved in regulation of intracellular Ca2+ for drug development:: Pharmacology of SEA0400, a specific inhibitor of the Na+-Ca2+ exchanger
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DOI：
10.1254/jphs.fmj04007x2
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发表时间：
2005-03-01
影响因子：
3.5
通讯作者：
Baba, A
中科院分区：
文献类型：
--
作者：
Matsuda, T;Koyama, Y;Baba, A
Na+-Ca ~（2+）交换器（NCX）参与细胞内Ca ~（2+）浓度的调节。为了阐明NCX的生理和病理作用，需要NCX的特异性抑制剂。我们已经开发了2-[4-[（2，5-二氟苯基）甲氧基]苯氧基]-5-乙氧基苯胺（SEA 0400），一种高效和选择性的NCX抑制剂。在抑制NCX的浓度范围内，SEA 0400对Ca ~（2+）通道、Na ~+通道、K ~+通道、去甲肾上腺素转运蛋白和14种受体的亲和力可忽略不计;并且它不影响储存操纵的Ca ~（2+）通道、Na ~+-H ~+交换器和包括Na ~+，K ~+-ATP酶和Ca ~（2+）-ATP酶在内的几种酶的活性。此外，最近的研究表明，SEA 0400减轻脑，心脏和肾脏的缺血再灌注损伤和大鼠脑中射频损伤诱导的水肿。这些结果表明，NCX在缺血再灌注损伤中起着关键作用，并可能成为治疗再灌注损伤相关疾病的靶分子。
The Na+-Ca2+ exchanger (NCX) is involved in regulation of intracellular Ca2+ concentration. A specific inhibitor of NCX has been required for clarification of the physiological and pathological roles of NCX. We have developed 2-[4-[(2,5-difluorophenyl)methoxy] phenoxy]-5-ethoxyaniline (SEA0400), a highly potent and selective inhibitor of NCX. SEA0400 in the concentration range that inhibits NCX exhibits negligible affinities for the Ca2+ channels, Na+ channels, K+ channels, noradrenaline transporter, and 14 receptors; and it does not affect the activities of the store-operated Ca2+ channel, Na+-H+ exchanger, and several enzymes including Na+, K+-ATPase and Ca2+-ATPase. Furthermore, recent studies show that SEA0400 attenuates ischemia-reperfusion injury in the brain, heart, and kidney and radiofrequency lesion-induced edema in rat brain. These findings suggest that NCX plays a key role in ischemia-reperfusion injury and may be a target molecule for treatment of reperfusion injury-related diseases.