Imenez Silva, Pedro H, Benabbas, Chahira, Chan, Kessara, Ludwig, Marie-Gabrielle, Gasser, Juerg Andreas, Arnett, Timothy, Bonny, Olivier, Seuwen, Klaus and Wagner, Carsten A. (2019) The H+-Activated Ovarian Cancer G Protein-Coupled Receptor 1 (OGR1) is responsible for Renal Calcium Loss during Acidosis. Kidney international. ISSN 1523-1755; 0085-2538

Abstract

ABSTRACT

Hypercalciuria is a common feature during metabolic acidosis. However, the mechanisms sensing acidosis and inducing increased urinary calcium excretion during acidosis are still unknown. Here we report that mice deficient for the Ovarian cancer G-protein coupled receptor 1 (OGR1 or Gpr68) did not excrete more calcium during chronic metabolic acidosis. Wild type (OGR1+/+) and OGR1-deficient mice (OGR1-/-) were subjected to standard chow (control) or 0.28 M NH4Cl in water for 1 day (acute metabolic acidosis) or 2 % NH4Cl in food for 7 days (chronic metabolic acidosis). OGR1 mRNA is ubiquitously expressed, including kidneys, and found along the entire nephron. No differences in responding to the acid load were observed in OGR1-/- mice, except for higher plasma [HCO3-] after 1 day. Bone mineral density and resorption activity of osteoclasts were similar between OGR1+/+ and OGR1-/- mice. Plasma PTH and Vitamin D3 levels were indistinguishable. However, the expression levels of key proteins for active transepithelial Ca2+ reabsorption in the distal convoluted tubule, TRPV5 and Calbindin-D28k were increased in OGR1-/- mice under metabolic acidosis. TRPV5 abundance was downregulated in wild type mice during metabolic acidosis but maintained at the same level in the absence of OGR1. OGR1-/- also exhibited higher NHE3 abundance when compared to OGR1+/+ under metabolic acidosis. In conclusion, OGR1 is a pH sensor involved in the hypercalciuria developed during metabolic acidosis and may regulate renal calcium excretion through modulation of proximal tubular NHE3 activity and regulation of the distal tubule TRPV5 calcium channel.

Item Type:	Article
Keywords:	OGR1, Renal Calcium, Acidosis,
Date Deposited:	21 Apr 2020 00:45
Last Modified:	21 Apr 2020 00:45
URI:	https://oak.novartis.com/id/eprint/32093