α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism.

Détails

Ressource 1Télécharger: BIB_93F2D96819D4.P001.pdf (12482.16 [Ko])
Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_93F2D96819D4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism.
Périodique
Journal of Clinical Investigation
Auteur(s)
Tokonami N., Morla L., Centeno G., Mordasini D., Ramakrishnan S.K., Nikolaeva S., Wagner C.A., Bonny O., Houillier P., Doucet A., Firsov D.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
123
Numéro
7
Pages
3166-3171
Langue
anglais
Notes
Publication types: Journal Article; PDF : Research Article
Résumé
Paracrine communication between different parts of the renal tubule is increasingly recognized as an important determinant of renal function. Previous studies have shown that changes in dietary acid-base load can reverse the direction of apical α-ketoglutarate (αKG) transport in the proximal tubule and Henle's loop from reabsorption (acid load) to secretion (base load). Here we show that the resulting changes in the luminal concentrations of αKG are sensed by the αKG receptor OXGR1 expressed in the type B and non-A-non-B intercalated cells of the connecting tubule (CNT) and the cortical collecting duct (CCD). The addition of 1 mM αKG to the tubular lumen strongly stimulated Cl--dependent HCO3- secretion and electroneutral transepithelial NaCl reabsorption in microperfused CCDs of wild-type mice but not Oxgr1-/- mice. Analysis of alkali-loaded mice revealed a significantly reduced ability of Oxgr1-/- mice to maintain acid-base balance. Collectively, these results demonstrate that OXGR1 is involved in the adaptive regulation of HCO3- secretion and NaCl reabsorption in the CNT/CCD under acid-base stress and establish αKG as a paracrine mediator involved in the functional coordination of the proximal and the distal parts of the renal tubule.
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/08/2013 9:17
Dernière modification de la notice
08/05/2019 22:12
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