Early aldosterone effect in distal colon by transcriptional regulation of ENaC subunits
Early aldosterone effect in distal colon by transcriptional regulation of ENaC subunits
复制标题
DOI：
10.1152/ajpgi.2000.278.5.g718
复制
发表时间：
2000-05-01
影响因子：
4.5
通讯作者：
Fromm, M
中科院分区：
文献类型：
--
作者：
Epple, HJ;Amasheh, S;Fromm, M
醛固酮诱导的钠吸收是由上皮钠离子通道(ENaC)介导的。这种“早期效应”并不是基于基因组对ENaC表达的调控，因为ENaC亚单位转录开始的时间晚于Na+转运。我们研究了大鼠早期(EDC)和晚期(LDC)远端结肠的电源性Na+吸收(J(Na))，以及在相同组织中ENaC亚单位的mRNA表达。在这两段细胞中，3 NM的醛固酮体外孵育8h可促进β-和γ-ENaC mRNA的表达，诱导的J(Na-)J(Na)是EDC的10倍。α-ENaC mRNA在EDC中无明显变化，而在LDC中呈下降趋势。在LDC中，β-和γ-ENaC mRNA在加入醛固酮后1h被诱导，而J(Na)在1h后明显增加。β-和γ-ENaC诱导和J(Na)刺激的时间相关性表明，醛固酮对远端结肠Na+吸收的早期影响是通过转录上调β和γ-ENaC的表达来实现的。
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 Ih 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.