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Am J Physiol Gastrointest Liver Physiol 278: G718-G724, 2000;
0193-1857/00 $5.00
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Vol. 278, Issue 5, G718-G724, May 2000

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

H. J. Epple1,2, S. Amasheh1, J. Mankertz2, M. Goltz3, J. D. Schulzke2, and M. Fromm1

Departments of 1 Clinical Physiology and 2 Gastroenterology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, 12200 Berlin; and 3 Department of Xenotransplantation, Robert Koch-Institut, 13353 Berlin, Germany

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 (JNa) 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 JNa. JNa 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 JNa 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 JNa stimulation suggests that the early aldosterone effect on Na+ absorption in distal colon is caused by transcriptional upregulation of beta - and gamma -ENaC expression.

epithelial sodium channel; segmental heterogeneity; mineralocorticoid receptor; glucocorticoid receptor; heterodimer


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