The proton-activated ovarian cancer G protein-coupled receptor 1 (OGR1) is responsible for renal calcium loss during acidosis.

Details

Serval ID
serval:BIB_70B7F359D061
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The proton-activated ovarian cancer G protein-coupled receptor 1 (OGR1) is responsible for renal calcium loss during acidosis.
Journal
Kidney international
Author(s)
Imenez Silva P.H., Katamesh-Benabbas C., Chan K., Pastor Arroyo E.M., Knöpfel T., Bettoni C., Ludwig M.G., Gasser J.A., Brandao-Burch A., Arnett T.R., Bonny O., Seuwen K., Wagner C.A.
ISSN
1523-1755 (Electronic)
ISSN-L
0085-2538
Publication state
Published
Issued date
05/2020
Peer-reviewed
Oui
Volume
97
Number
5
Pages
920-933
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Hypercalciuria is a common feature during metabolic acidosis and associates to nephrolithiasis and nephrocalcinosis. The mechanisms sensing acidosis and inducing increased urinary calcium excretion are still unknown. Here we tested whether mice deficient for proton-activated Ovarian cancer G-protein coupled receptor 1 (OGR1 or Gpr68) have reduced urinary excretion of calcium during chronic metabolic acidosis. In the kidney, OGR1 mRNA was found in cells of the glomerulus, proximal tubule, and interstitium including endothelial cells. Wild type (OGR1 <sup>+/+</sup> ) and OGR1 knockout (OGR1 <sup>-/-</sup> ) mice were given standard chow without (control) or loaded with ammonium chloride for one or seven days to induce acute or chronic metabolic acidosis, respectively. No differences in responding to the acid load were observed in the knockout mice, except for higher plasma bicarbonate after one day. Bone mineral density, resorption activity of osteoclasts, and urinary deoxypyridinoline were similar between genotypes. During metabolic acidosis the expression levels of key proteins involved in calcium reabsorption, i.e. the sodium/proton exchanger (NHE3), the epithelial calcium-selective channel TRPV5, and the vitamin D-dependent calcium binding protein calbindin-D28k were all higher in the knockout mice compared to wild type mice. This is consistent with the previous demonstration that OGR1 reduces NHE3 activity in proximal tubules of mice. Wild-type mice displayed a non-linear positive association between urinary proton and calcium excretion which was lost in the knockout mice. Thus, OGR1 is a pH sensor involved in the hypercalciuria of metabolic acidosis by controlling NHE3 activity in the proximal tubule. Hence, novel drugs modulating OGR1 activity may improve renal calcium handling.
Keywords
GPCR, NHE3, acidosis, calcium, hypercalciuria, proton sensing
Pubmed
Web of science
Create date
02/04/2020 17:13
Last modification date
17/02/2021 7:27
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