Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal sodium retention is responsible for ascites and edema in nephrotic syndrome. In puromycin aminonucleoside (PAN)-induced nephrosis, sodium retention originates in part from the collecting duct, and it is associated with increased Na,K-ATPase activity in the cortical collecting duct (CCD). The aims of this study were to evaluate whether the outer medullary collecting duct (OMCD) also participates to sodium retention and to determine the mechanisms responsible for stimulation of Na,K-ATPase in CCD. PAN nephrosis increased Na,K-ATPase activity in the CCD but not in OMCD. The two-fold increase of Na,K-ATPase activity in CCD was associated with two-fold increases in the number of alpha and beta Na,K-ATPase subunits mRNA determined by quantitative RT-PCR and of the total amount of Na,K-ATPase alpha subunits estimated by Western blotting. PAN nephrosis also increased two-fold the amount of Na,K-ATPase alpha subunit at the basolateral membrane of CCD principal cells, as determined by Western blotting after biotinylation and streptavidin precipitation and by immunofluorescence. The intracellular pool of latent Na,K-ATPase units also increased in size and was no longer recruitable by vasopressin and cAMP. This unresponsiveness of the intracellular pool of Na,K-ATPase to vasopressin was not the result of any alteration of the molecular and functional expression of the vasopressin V(2) receptor/adenylyl cyclase (AC) complex. It is concluded that PAN nephrosis (1) does not alter sodium reabsorption in OMCD, (2) is associated with increased synthesis and membrane expression of Na,K-ATPase in the CCD, and (3) alters the normal trafficking of intracellular Na,K-ATPase units to the basolateral membrane.
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PMID:Increased synthesis and avp unresponsiveness of Na,K-ATPase in collecting duct from nephrotic rats. 1167

Aldosterone controls extracellular volume and blood pressure by regulating Na(+) reabsorption across epithelial cells of the aldosterone-sensitive distal nephron (ASDN). This effect is mediated by a coordinate action on the luminal channel ENaC (generally rate limiting) and the basolateral Na,K-ATPase. Long-term effects of aldosterone (starting within 3 to 6 hours and increasing over days) are mediated by the direct and indirect induction of stable elements of the Na(+) transport machinery (e.g., Na,K-ATPase alpha subunit), whereas short-term effects appear to be mediated by the upregulation of short-lived elements of the machinery (e.g., ENaC alpha subunit) and of regulatory proteins, such as the serum- and glucocorticoid-regulated kinase SGK1. We have recently shown that in cortical collecting duct (CCD) from adrenalectomized (ADX) rats, the increase in Na,K-ATPase activity (approximately threefold in 3 h), induced by a single aldosterone injection, can be fully accounted for by the increase in Na,K-ATPase cell-surface expression. Using the model cell line mpkCCD(cl4), we showed that the parallel increase in Na,K-ATPase function [assessed by Na(+) pump current (I(p)) measurements] and cell-surface expression depends on transcription and translation, and that it is not secondary to a change in apical Na(+) influx. As a first approach to address the question whether the aldosterone-induced regulatory protein SGK1 might play a role in mediating Na,K-ATPase translocation, we have used the Xenopus laevis expression system. SGK1 coexpression indeed increased both the Na(+) pump current and the surface expression of pumps containing the rat alpha1 subunits. In summary, aldosterone controls Na(+) reabsorption in the short term not only by regulating the apical cell-surface expression of ENaC but also by coordinately acting on the basolateral cell-surface expression of the Na,K-ATPase. Results obtained in the Xenopus oocyte expression system suggest the possibility that this effect could be mediated in part by the aldosterone-induced kinase SGK1.
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PMID:Short-term aldosterone action on Na,K-ATPase surface expression: role of aldosterone-induced SGK1? 1276 89