A peek into Epac physiology in the kidney.
A peek into Epac physiology in the kidney.
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肾脏 Epac 生理学一瞥。
DOI：
10.1152/ajprenal.00373.2019
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Pochynyuk,Oleh
中科院分区：
文献类型：
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作者：
Tomilin,ViktorN;Pochynyuk,Oleh
CAMP是影响肾小管水-电解质转运的众多内分泌信号的关键第二信使。CAMP直接激活的交换蛋白(EPAC)是最近发现的cAMP下游效应蛋白，与经典的cAMP靶标蛋白激酶A具有相同的亲和力。EPAC的两种异构体Epac1和Epac2在肾上皮细胞中大量表达，它们被认为调节水和电解质的运输，特别是在近端小管和集合管。最近对缺乏Epac1和Epac2的小鼠的肾脏表型的表征表明，EPAC信号级联在尿液浓度以及Na+和尿素排泄中起着关键作用。在这篇综述中，我们旨在批判性地总结EPAC与肾功能相关性的现有知识，并讨论基于EPAC的策略在调节全身水-电解质稳态中的适用性。
cAMP is a critical second messenger of numerous endocrine signals affecting water-electrolyte transport in the renal tubule. Exchange protein directly activated by cAMP (Epac) is a relatively recently discovered downstream effector of cAMP, having the same affinity to the second messenger as protein kinase A, the classical cAMP target. Two Epac isoforms, Epac1 and Epac2, are abundantly expressed in the renal epithelium, where they are thought to regulate water and electrolyte transport, particularly in the proximal tubule and collecting duct. Recent characterization of renal phenotype in mice lacking Epac1 and Epac2 revealed a critical role of the Epac signaling cascade in urinary concentration as well as in Na+and urea excretion. In this review, we aim to critically summarize current knowledge of Epac relevance for renal function and to discuss the applicability of Epac-based strategies in the regulation of systemic water-electrolyte homeostasis.