Article: article from journal or magazin.
ERK1/2 controls Na,K-ATPase activity and transepithelial sodium transport in the principal cell of the cortical collecting duct of the mouse kidney.
Journal of Biological Chemistry
The collecting duct of normal kidney exhibits significant activity of the MEK1/2-ERK1/2 pathway as shown in vivo by immunostaining of phosphorylated active ERK1/2 (pERK1/2). The MEK1/2-ERK1/2 pathway controls many different ion transports both in proximal and distal nephron, raising the question of whether this pathway is involved in the basal and/or hormone-dependent transepithelial sodium reabsorption in the principal cell of the cortical collecting duct (CCD), a process mediated by the apical epithelial sodium channel and the basolateral sodium pump (Na,K-ATPase). To answer this question we used ex vivo microdissected CCDs from normal mouse kidney or in vitro cultured mpkCCDcl4 principal cells. Significant basal levels of pERK1/2 were observed ex vivo and in vitro. Aldosterone and vasopressin, known to up-regulate sodium reabsorption in CCDs, did not change ERK1/2 activity either ex vivo or in vitro. Basal and aldosterone- or vasopressin-stimulated sodium transport was down-regulated by the MEK1/2 inhibitor PD98059, in parallel with a decrease in pERK1/2 in vitro. The activity of Na,K-ATPase but not that of epithelial sodium channel was inhibited by MEK1/2 inhibitors in both unstimulated and aldosterone- or vasopressin-stimulated CCDs in vitro. Cell surface biotinylation showed that intrinsic activity rather than cell surface expression of Na,K-ATPase was controlled by pERK1/2. PD98059 also significantly inhibited the activity of Na,K-ATPase ex vivo. Our data demonstrate that the ERK1/2 pathway controls Na,K-ATPase activity and transepithelial sodium transport in the principal cell and indicate that basal constitutive activity of the ERK1/2 pathway is a critical component of this control.
Aldosterone/metabolism, Animals, Biological Transport, Biotinylation, Blotting, Western, Cell Membrane/metabolism, Cells, Cultured, Dose-Response Relationship, Drug, Electrophysiology, Enzyme Inhibitors/pharmacology, Flavonoids/pharmacology, Kidney/metabolism, Kidney Tubules, Collecting/metabolism, Ligands, Male, Mice, Mitogen-Activated Protein Kinase 1/physiology, Mitogen-Activated Protein Kinase 3/physiology, Nephrons/metabolism, Phosphorylation, Sodium/metabolism, Sodium-Potassium-Exchanging ATPase/chemistry, Sodium-Potassium-Exchanging ATPase/metabolism, Time Factors, Up-Regulation, Vasopressins/metabolism
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