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

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Version: Author's accepted manuscript
Serval ID
serval:BIB_93F2D96819D4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism.
Journal
Journal of Clinical Investigation
Author(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
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
123
Number
7
Pages
3166-3171
Language
english
Notes
Publication types: Journal Article; PDF : Research Article
Abstract
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
Yes
Create date
18/08/2013 9:17
Last modification date
20/10/2020 11:08
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