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

当前位置： X-MOL 学术 › Kidney Int. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

The proton-activated ovarian cancer G protein-coupled receptor 1 (OGR1) is responsible for renal calcium loss during acidosis.
Kidney International ( IF 14.8 ) Pub Date : 2019-12-25 , DOI: 10.1016/j.kint.2019.12.006
Pedro Henrique Imenez Silva ₁ , Chahira Katamesh-Benabbas ₁ , Kessara Chan ₁ , Eva Maria Pastor Arroyo ₁ , Thomas Knöpfel ₂ , Carla Bettoni ₁ , Marie-Gabrielle Ludwig ₃ , Jürg A Gasser ₃ , Andrea Brandao-Burch ₄ , Timothy R Arnett ₄ , Olivier Bonny ₅ , Klaus Seuwen ₃ , Carsten Alexander Wagner ₁

Affiliation

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+/+) and OGR1 knockout (OGR1-/-) 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.

中文翻译：

质子激活的卵巢癌 G 蛋白偶联受体 1 (OGR1) 是酸中毒期间肾钙丢失的原因。

高钙尿症是代谢性酸中毒的常见特征，与肾结石和肾钙质沉着有关。感知酸中毒和诱导尿钙排泄增加的机制仍然未知。在这里，我们测试了缺乏质子激活的卵巢癌 G 蛋白偶联受体 1（OGR1 或 Gpr68）的小鼠在慢性代谢性酸中毒期间是否减少了尿中钙的排泄。在肾脏中，OGR1 mRNA 存在于肾小球、近端小管和间质细胞（包括内皮细胞）中。野生型 (OGR1+/+) 和 OGR1 敲除 (OGR1-/-) 小鼠分别给予标准食物（对照）或氯化铵负荷 1 或 7 天，以分别诱导急性或慢性代谢性酸中毒。在敲除小鼠中没有观察到对酸负荷的反应差异，一天后血浆碳酸氢盐升高除外。基因型之间的骨矿物质密度、破骨细胞的再吸收活性和尿脱氧吡啶啉相似。在代谢性酸中毒期间，参与钙重吸收的关键蛋白，即钠/质子交换剂 (NHE3)、上皮钙选择性通道 TRPV5 和维生素 D 依赖性钙结合蛋白 calbindin-D28k 的表达水平在敲除中均较高小鼠与野生型小鼠相比。这与之前的证明一致，即 OGR1 降低了小鼠近端小管中的 NHE3 活性。野生型小鼠在敲除小鼠中丢失了尿质子和钙排泄之间的非线性正相关。因此，OGR1 是一种 pH 传感器，通过控制近端小管中的 NHE3 活性参与代谢性酸中毒的高钙尿症。因此，调节 OGR1 活性的新药可能会改善肾钙处理。

更新日期：2019-12-25

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11