title: Increased synthesis and avp unresponsiveness of Na,K-ATPase in collecting duct from nephrotic rats.
abstract: 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.
authors.affiliation: Service de Néphrologie Pédiatrique, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France.|Laboratoire de Biologie Intégrée des Cellules Rénales, Service de Biologie Cellulaire, Commissariat à l'Energie Atomique, Gif sur Yvette, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.affiliation: Fondation pour Recherches Médicales, Laboratoire de Néphrologie, Geneva, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Gonin
authors.affiliation: Fondation pour Recherches Médicales, Laboratoire de Néphrologie, Geneva, Switzerland.
authors.forename: Einath
authors.initials: E
authors.lastname: Zolty
authors.affiliation: Laboratoire de Biologie Intégrée des Cellules Rénales, Service de Biologie Cellulaire, Commissariat à l'Energie Atomique, Gif sur Yvette, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Cheval
authors.affiliation: Fondation pour Recherches Médicales, Laboratoire de Néphrologie, Geneva, Switzerland.
authors.forename: Martine
authors.initials: M
authors.lastname: Rousselot
authors.affiliation: Fondation pour Recherches Médicales, Laboratoire de Néphrologie, Geneva, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Martin
authors.affiliation: Service de Biologie Cellulaire, Commissariat à l'Energie Atomique, Gif sur Yvette, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Verbavatz
authors.affiliation: Fondation pour Recherches Médicales, Laboratoire de Néphrologie, Geneva, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Féraille
authors.affiliation: Laboratoire de Biologie Intégrée des Cellules Rénales, Service de Biologie Cellulaire, Commissariat à l'Energie Atomique, Gif sur Yvette, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Doucet
mesh_terms: D000042:Absorption; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009401:Nephrosis / Q000139:chemically induced* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D011692:Puromycin Aminonucleoside; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology
chemical_list: D012076:Renal Agents; D001127:Arginine Vasopressin; D011692:Puromycin Aminonucleoside; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase