ENaC is regulated by natriuretic peptide receptor-dependent cGMP signaling
ENaC is regulated by natriuretic peptide receptor-dependent cGMP signaling
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DOI：
10.1152/ajprenal.00638.2012
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发表时间：
2013-04-01
影响因子：
4.2
通讯作者：
Bao, Hui-Fang
中科院分区：
文献类型：
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作者：
Guo, Lai-Jing;Alli, Abdel A.;Bao, Hui-Fang
郭L，阿利AA，伊顿DC，鲍H. ENaC受利钠肽受体依赖性cGMP信号传导调节。美国肾脏生理学杂志304：F930-F937，2013年。首次发表于2013年1月16日; doi：10.1152/ajprenal.00638.2012.-位于极化上皮细胞顶膜的上皮钠通道（ENaCs）受第二信使鸟苷3 '，5'-环一磷酸（cGMP）调节。这种调节的机制尚未完全确定。鸟苷酸环化酶响应于各种细胞内和细胞外信号而合成cGMP。我们研究了在爪蟾2F 3细胞中鸟苷酸环化酶的利钠肽依赖性激活对ENaC活性的调节。共聚焦显微镜研究表明，利钠肽受体（NPR），包括那些耦合到鸟苷酸环化酶，在2F 3细胞的顶膜表达。使用2F 3细胞的单通道膜片钳研究显示，心房钠尿肽（ANP）或8-（4-氯苯硫基）-cGMP，而不是C型钠尿肽或cANP，降低ENaC的开放概率。这表明NPR-A，而不是NPR-B或NPR-C，参与了利钠肽介导的ENaC活性调节。此外，这是可能的，涉及cGMP和一氧化氮（NO）的信号通路参与了这一机制，因为可溶性鸟苷酸环化酶，蛋白激酶G，诱导型NO合酶，或NO清除剂的抑制剂阻断或降低ANP对ENaC活性的影响。
Guo L, Alli AA, Eaton DC, Bao H. ENaC is regulated by natriuretic peptide receptor dependent cGMP signaling. Am J Physiol Renal Physiol 304: F930-F937, 2013. First published January 16, 2013; doi:10.1152/ajprenal.00638.2012.-Epithelial sodium channels (ENaCs) located at the apical membrane of polarized epithelial cells are regulated by the second messenger guanosine 3',5'-cyclic monophosphate (cGMP). The mechanism for this regulation has not been completely characterized. Guanylyl cyclases synthesize cGMP in response to various intracellular and extracellular signals. We investigated the regulation of ENaC activity by natriuretic peptide-dependent activation of guanylyl cyclases in Xenopus 2F3 cells. Confocal microscopy studies show natriuretic peptide receptors (NPRs), including those coupled to guanylyl cyclases, are expressed at the apical membrane of 2F3 cells. Single-channel patch-clamp studies using 2F3 cells revealed that atrial natriuretic peptide (ANP) or 8-(4-chlorophenylthio)-cGMP, but not C-type natriuretic peptide or cANP, decreased the open probability of ENaC. This suggests that NPR-A, but not NPR-B or NPR-C, is involved in the natriuretic peptide-mediated regulation of ENaC activity. Also, it is likely that a signaling pathway involving cGMP and nitric oxide (NO) are involved in this mechanism, since inhibitors of soluble guanylyl cyclase, protein kinase G, inducible NO synthase, or an NO scavenger blocked or reduced the effect of ANP on ENaC activity.