title: Mechanism of control of Na,K-ATPase in principal cells of the mammalian collecting duct.
abstract: The collecting duct is the site of final Na reabsorption according to Na balance requirements. Using isolated rat cortical collecting ducts (CCD) and mpkCCD(cl4) cells, a mouse cortical collecting duct cell line, we have studied the physiological control of Na,K-ATPase, the key enzyme that energizes Na reabsorption. Aldosterone, a major regulator of Na transport by the collecting duct, stimulates Na,K-ATPase activity through both recruitment of intracellular pumps and increased total amounts of Na pump subunits. This effect is observed after a lag time of 1 hour and is independent of Na entry through ENaC, but requires de novo transcription and translation. Vasopressin and cAMP, its second messenger, stimulate Na,K-ATPase activity within minutes through translocation of Na pumps from a brefeldin A-sensitive intracellular pool to the plasma membrane. Dysregulation of collecting duct Na,K-ATPase activity is at least in part responsible of the Na retention observed in nephritic syndrome. In this setting, Na,K-ATPase activity and subunit synthesis are specifically increased in CCD. In conclusion, aldosterone, vasopressin, and intracellular Na control the cell surface expression of Na,K-ATPase and translocation from intracellular stores is a major mechanism of regulation of Na,K-ATPase activity in collecting duct principal cells.
authors.affiliation: Division de Néphrologie, Fondation pour Recherches Médicales, CH-1211 Genève 4, Switzerland. Eric.Feraille@medecine.unige.ch
authors.forename: Eric
authors.initials: E
authors.lastname: Féraille
authors.forename: David
authors.initials: D
authors.lastname: Mordasini
authors.forename: Sandrine
authors.initials: S
authors.lastname: Gonin
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.forename: Alain
authors.initials: A
authors.lastname: Doucet
authors.forename: Alain
authors.initials: A
authors.lastname: Vandewalle
authors.forename: Vanessa
authors.initials: V
authors.lastname: Summa
authors.forename: François
authors.initials: F
authors.lastname: Verrey
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Martin
mesh_terms: D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000201:enzymology / Q000502:physiology*; D008322:Mammals; D008954:Models, Biological; D009404:Nephrotic Syndrome / Q000201:enzymology / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D014667:Vasopressins; D000450:Aldosterone; D012964:Sodium; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase