Escoubet B, Coureau C, Bonvalet J P, Farman N
Institut Fédératif de Recherche Cellules Epithéliales, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Am J Physiol. 1997 May;272(5 Pt 1):C1482-91. doi: 10.1152/ajpcell.1997.272.5.C1482.
Distal colon and renal cortical collecting ducts are major effectors of aldosterone-dependent Na homeostasis. Na is absorbed by entry through an apical amiloride-sensitive Na channel and extruded by Na-K-ATPase at the basolateral membrane. Using a ribonuclease protection assay, we studied, in vivo, aldosterone regulation of alpha-, beta-, gamma-subunits of the rat epithelial Na channel (rENaC) and alpha 1- and beta 1-subunits of Na-K-ATPase. In the kidney, Na-K-ATPase mRNAs were also assayed over discrete tubular segments by in situ hybridization. In rat colon, all three rENaC mRNAs were decreased by adrenalectomy, with a major effect on beta- and gamma-subunits, and were restored with 7 days, but not 2 days, of aldosterone treatment; in the kidney, however, only alpha-transcripts varied. Na-K-ATPase alpha 1- and beta 1-subunit mRNAs in both organs were not (in the case of the beta 1-subunit) or were mildly (in the case of the alpha 1-subunit) affected after adrenalectomy. Our conclusions are as follows: 1) Transcripts of rENaC and Na-K-ATPase subunits are not coordinately regulated by aldosterone in vivo; i.e., modulation involves mainly the Na channel, not Na-K-ATPase; the effect is not of comparable magnitude on each subunit mRNA and differs between tissues. 2) The delay of the aldosterone effect on transcripts is much longer than that required to restore normal Na transport in adrenalectomized rats, indicating that rENaC and Na-K-ATPase subunit transcript levels may depend on unidentified early aldosterone-induced proteins.
远端结肠和肾皮质集合管是醛固酮依赖性钠稳态的主要效应器。钠通过顶端氨氯地平敏感的钠通道进入细胞被吸收，并由基底外侧膜上的钠钾ATP酶排出。我们使用核糖核酸酶保护分析方法，在体内研究了醛固酮对大鼠上皮钠通道（rENaC）的α、β、γ亚基以及钠钾ATP酶的α1和β1亚基的调节作用。在肾脏中，还通过原位杂交在离散的肾小管节段检测了钠钾ATP酶的mRNA。在大鼠结肠中，肾上腺切除术后所有三种rENaC mRNA均减少，对β和γ亚基影响较大，醛固酮治疗7天可恢复，但2天不能恢复；然而在肾脏中，只有α转录本发生变化。两个器官中的钠钾ATP酶α1和β1亚基mRNA在肾上腺切除术后未受影响（β1亚基的情况）或受到轻微影响（α1亚基的情况）。我们的结论如下：1）rENaC和钠钾ATP酶亚基的转录本在体内不受醛固酮的协同调节；即调节主要涉及钠通道，而非钠钾ATP酶；对每个亚基mRNA的影响程度不同，且在不同组织间存在差异。2）醛固酮对转录本的作用延迟远长于恢复肾上腺切除大鼠正常钠转运所需的时间，表明rENaC和钠钾ATP酶亚基转录本水平可能依赖于未确定的早期醛固酮诱导蛋白。
