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

Tokonami, Natsuko; Morla, Luciana; Centeno, Gabriel; Mordasini, David; Ramakrishnan, Suresh Krishna; Nikolaeva, Svetlana; Wagner, Carsten A; Bonny, Olivier; Houillier, Pascal; Doucet, Alain; Firsov, Dmitri (2013). α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism. Journal of clinical investigation, 123(7), pp. 3166-71. Ann Arbor, Mich.: American Society for Clinical Investigation 10.1172/JCI67562

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Mordasini, David

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:42

Last Modified:

22 Jul 2015 09:52

Publisher DOI:

10.1172/JCI67562

PubMed ID:

23934124

Web of Science ID:

000321316700043

BORIS DOI:

10.7892/boris.17514

URI:

https://boris.unibe.ch/id/eprint/17514 (FactScience: 225296)

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