Noncoordinate regulation of epithelial Na channel and Na pump subunit mRNAs in kidney and colon by aldosterone

Abstract

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.

Corticosteroid regulation of amiloride-sensitive sodium-channel subunit mRNA expression in mouse kidney

“…Previous studies have found no clear corticosteroid regulation of ENaC or in rat kidney (Renard et al 1995, Asher et al 1996, Escoubet et al 1997, Stokes & Sigmund 1998. These effects on ENaC , and especially , mRNA expression were relatively small and limited to specific renal regions, and thus would probably not have been seen in analyses of the whole kidney.…”

“…These effects on ENaC , and especially , mRNA expression were relatively small and limited to specific renal regions, and thus would probably not have been seen in analyses of the whole kidney. Moreover, previous studies examining the effects of corticosteroid were of shorter duration and there is evidence, in A6 kidney cells (Middleton et al 1998) (and rat colon (Escoubet et al 1997)) that ENaC and mRNA changes may develop over at least several days. These differences may explain the lack of significant changes in renal ENaC or expression in previous in vivo studies.…”

“…This is the first such study of ENaC regulation in mouse. Previous work has examined kidney expression of ENaC in the rat (Renard et al 1995, Asher et al 1996, Escoubet et al 1997, Stokes & Sigmund 1998, with modest upregulation of ENaC being reported. However, mineralocorticoid doses used in those rat studies were largely in the pharmacological range (5-to 15-fold greater) (Renard et al 1995, Asher et al 1996, Stokes & Sigmund 1998.…”

Chronic Exposure to Vasopressin Upregulates ENaC and Sodium Transport in the Rat Renal Collecting Duct and Lung

“…This pattern is similar to that reported in a CD cell line exposed to vasopressin in vitro for several hours 31 and to that observed in the colon after in vivo aldosterone or dexamethasone treatment for several days. 8,9 This suggests that the long-term hormone-dependent regulation of ENaC expression is achieved mainly by changes in the abundance of these 2 subunits and that ␣-subunit abundance (mRNA or protein) is either not rate limiting for assembly of ENaC channels or regulated by other mechanisms.…”

“…In the distal colon, a large increase in ␤-and ␥-subunit transcripts is observed in response to steroid treatment, whereas expression of ␣-subunit mRNA shows little variation. 8 -10 In contrast, in the kidney, aldosterone affects only the expression of ␣-subunit transcript or protein, 9,11,12 although some investigators found no effect of this hormone on subunit abundance. 4,8,13 Moreover, transgenic mice lacking the mineralocorticoid receptor exhibit a normal abundance of mRNAs encoding ENaC subunits in the kidney.…”