title: Pendrin regulation in mouse kidney primarily is chloride-dependent.
abstract: Recent studies indicate that pendrin, an apical Cl-/HCO3- exchanger, mediates chloride reabsorption in the connecting tubule and the cortical collecting duct and therefore is involved in extracellular fluid volume regulation. The purpose of this study was to test whether pendrin is regulated in vivo primarily by factors that are associated with changes in renal chloride transport, by aldosterone, or by the combination of both determinants. For achievement of this goal, pendrin protein abundance was studied by semiquantitative immunoblotting in different mouse models with altered aldosterone secretion or tubular chloride transport, including NaCl loading, hydrochlorothiazide administration, NaCl co-transporter knockout mice, and mice with Liddle's mutation. The parallel regulation of the aldosterone-regulated epithelial sodium channel (ENaC) was examined as a control for biologic effects of aldosterone. Major changes in pendrin protein expression were found in experimental models that are associated with altered renal chloride transport, whereas no significant changes were detected in pendrin protein abundance in models with altered aldosterone secretion. Moreover, in response to hydrochlorothiazide administration, pendrin was downregulated despite a marked secondary hyperaldosteronism. In contrast, alpha-ENaC was markedly upregulated, and the molecular weight of a large fraction of gamma-ENaC subunits was shifted from 85 to 70 kD, consistent with previous results from rat models with elevated plasma aldosterone levels. These results suggest that factors that are associated with changes in distal chloride delivery govern pendrin expression in the connecting tubule and cortical collecting duct.
authors.affiliation: INSERM U652, IFR58, Institut des Cordeliers, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Vallet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Picard
authors.forename: Dominique
authors.initials: D
authors.lastname: Loffing-Cueni
authors.forename: Marinos
authors.initials: M
authors.lastname: Fysekidis
authors.forename: May
authors.initials: M
authors.lastname: Bloch-Faure
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.forename: Sylvie
authors.initials: S
authors.lastname: Breton
authors.forename: Pierre
authors.initials: P
authors.lastname: Meneton
authors.forename: Johannes
authors.initials: J
authors.lastname: Loffing
authors.forename: Peter S
authors.initials: PS
authors.lastname: Aronson
authors.forename: Régine
authors.initials: R
authors.lastname: Chambrey
authors.forename: Dominique
authors.initials: D
authors.lastname: Eladari
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D027963:Chloride-Bicarbonate Antiporters / Q000032:analysis* / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000008:administration & dosage / Q000378:metabolism*; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D015151:Immunoblotting; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012964:Sodium / Q000378:metabolism
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D053503:Epithelial Sodium Channels; D006852:Hydrochlorothiazide; D000450:Aldosterone; D012964:Sodium