The connecting tubule is the main site of the furosemide-induced urinary acidification by the vacuolar H+-ATPase

Détails

ID Serval
serval:BIB_E610FA2FD4D0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The connecting tubule is the main site of the furosemide-induced urinary acidification by the vacuolar H+-ATPase
Périodique
Kidney International
Auteur(s)
Kovacikova  J., Winter  C., Loffing-Cueni  D., Loffing  J., Finberg  K. E., Lifton  R. P., Hummler  E., Rossier  B., Wagner  C. A.
ISSN
0085-2538
Statut éditorial
Publié
Date de publication
11/2006
Peer-reviewed
Oui
Volume
70
Numéro
10
Pages
1706-16
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Nov
Résumé
Final urinary acidification is achieved by electrogenic vacuolar H(+)-ATPases expressed in acid-secretory intercalated cells (ICs) in the connecting tubule (CNT) and the cortical (CCD) and initial medullary collecting duct (MCD), respectively. Electrogenic Na(+) reabsorption via epithelial Na(+) channels (ENaCs) in the apical membrane of the segment-specific CNT and collecting duct cells may promote H(+)-ATPases-mediated proton secretion by creating a more lumen-negative voltage. The exact localization where this supposed functional interaction takes place is unknown. We used several mouse models performing renal clearance experiments and assessed the furosemide-induced urinary acidification. Increasing Na(+) delivery to the CNT and CCD by blocking Na(+) reabsorption in the thick ascending limb with furosemide enhanced urinary acidification and net acid excretion. This effect of furosemide was abolished with amiloride or benzamil blocking ENaC action. In mice deficient for the IC-specific B1 subunit of the vacuolar H(+)-ATPase, furosemide led to only a small urinary acidification. In contrast, in mice with a kidney-specific inactivation of the alpha subunit of ENaC in the CCD and MCD, but not in the CNT, furosemide alone and in combination with hydrochlorothiazide induced normal urinary acidification. These results suggest that the B1 vacuolar H(+)-ATPase subunit is necessary for the furosemide-induced acute urinary acidification. Loss of ENaC channels in the CCD and MCD does not affect this acidification. Thus, functional expression of ENaC channels in the CNT is sufficient for furosemide-stimulated urinary acidification and identifies the CNT as a major segment in electrogenic urinary acidification.
Mots-clé
Acid-Base Equilibrium/*drug effects/physiology Amiloride/pharmacokinetics/pharmacology Animals Diuretics/pharmacokinetics/*pharmacology Epithelial Sodium Channel/genetics/metabolism Furosemide/pharmacokinetics/*pharmacology Gene Expression Regulation/drug effects/genetics Gene Expression Regulation, Enzymologic/drug effects/genetics Hydrochlorothiazide/pharmacokinetics/pharmacology Hydrogen-Ion Concentration Kidney Tubules, Collecting/metabolism Kidney Tubules, Distal/*drug effects/metabolism Metabolic Clearance Rate/drug effects/physiology Mice Mice, Knockout Nephrons/drug effects/physiology Proton-Translocating ATPases/genetics/*metabolism Water-Electrolyte Balance/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:01
Dernière modification de la notice
20/08/2019 17:09
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