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醛固酮通过对上皮钠通道(ENaC)亚基的转录调控对远端结肠产生早期效应。

Early aldosterone effect in distal colon by transcriptional regulation of ENaC subunits.

作者信息

Epple H J, Amasheh S, Mankertz J, Goltz M, Schulzke J D, Fromm M

机构信息

Department of Clinical Physiology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, 12200 Berlin, Germany.

出版信息

Am J Physiol Gastrointest Liver Physiol. 2000 May;278(5):G718-24. doi: 10.1152/ajpgi.2000.278.5.G718.

DOI:10.1152/ajpgi.2000.278.5.G718
PMID:10801264
Abstract

Aldosterone-induced sodium absorption is mediated by the epithelial Na(+) channel (ENaC). It is thought that the "early effect" is not based on genomic regulation of ENaC expression, because ENaC subunit transcription was reported to start later than Na(+) transport. We investigated electrogenic Na(+) absorption (J(Na)) and, in identical tissues, mRNA expression of ENaC subunits in early (EDC) and late (LDC) distal colon of the rat. In both segments, 8-h in vitro incubation with 3 nM aldosterone enhanced expression of beta- and gamma-ENaC mRNA and induced J(Na). J(Na) was 10 times higher in LDC than in EDC. alpha-ENaC mRNA was unchanged in EDC, whereas it decreased in LDC. In LDC, beta- and gamma-ENaC mRNA was induced 1 h after aldosterone addition, whereas J(Na) became apparent >1 h later. Downregulation of alpha-ENaC mRNA did not take part in acute regulation because it started after a lag time of 3 h. Time correlation of beta- and gamma-ENaC induction and J(Na) stimulation suggests that the early aldosterone effect on Na(+) absorption in distal colon is caused by transcriptional upregulation of beta- and gamma-ENaC expression.

摘要

醛固酮诱导的钠吸收由上皮钠通道(ENaC)介导。据认为,“早期效应”并非基于ENaC表达的基因组调控,因为据报道ENaC亚基转录开始的时间晚于钠转运。我们研究了大鼠远端结肠早期(EDC)和晚期(LDC)中电生性钠吸收(J(Na))以及相同组织中ENaC亚基的mRNA表达。在这两个节段中,用3 nM醛固酮进行8小时的体外孵育可增强β-和γ-ENaC mRNA的表达并诱导J(Na)。LDC中的J(Na)比EDC中的高10倍。α-ENaC mRNA在EDC中未发生变化,而在LDC中则下降。在LDC中,添加醛固酮1小时后β-和γ-ENaC mRNA被诱导,而J(Na)在1小时后才明显出现。α-ENaC mRNA的下调不参与急性调节,因为它在3小时的延迟时间后才开始。β-和γ-ENaC诱导与J(Na)刺激的时间相关性表明,醛固酮对远端结肠钠吸收的早期效应是由β-和γ-ENaC表达的转录上调引起的。

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