CLONING AND FUNCTIONAL EXPRESSION OF A RAT-KIDNEY EXTRACELLULAR CALCIUM POLYVALENT CATION-SENSING RECEPTOR
CLONING AND FUNCTIONAL EXPRESSION OF A RAT-KIDNEY EXTRACELLULAR CALCIUM POLYVALENT CATION-SENSING RECEPTOR
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DOI：
10.1073/pnas.92.1.131
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发表时间：
1995-01-03
影响因子：
11.1
通讯作者：
HEBERT, SC
中科院分区：
文献类型：
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作者：
RICCARDI, D;PARK, J;HEBERT, SC
维持稳定的细胞外离子钙浓度取决于许多特化细胞（例如，甲状旁腺和某些肾上皮细胞）。我们最近确定了另一个G蛋白偶联受体（BoPCaR 1）从牛甲状旁腺，响应细胞外Ca 2+的变化在毫摩尔范围内，并提供了一个关键的机制，调节甲状旁腺激素的分泌。利用同源性分析的方法，我们从大鼠肾脏中分离到了一个编码细胞外Ca ~（2+）/多价阳离子敏感受体（RaKCaR）的cDNA，该蛋白与BoPCaR 1受体有92%的同源性，具有G蛋白偶联受体的特征，其之前是一个大的亲水性细胞外NH 2末端，据信参与阳离子结合，注射RaKCaR cRNA的非洲爪蟾卵母细胞对细胞外Ca 2+，Mg 2+，Gd 3+，和新霉素的肌醇磷脂依赖性，细胞内Ca 2+诱导的Cl-电流的特征性激活。在大鼠肾脏中，北方分析显示4和7 kb的RaKCaR转录本，原位杂交显示定位主要在外髓质和皮质髓射线。我们的研究结果提供了重要的见解细胞外Ca 2 +/多价阳离子敏感受体在大鼠肾脏的分子结构，并提供了另一个基础上，了解细胞外二价阳离子在调节肾功能的矿物质代谢的作用。
The maintenance of a stable extracellular concentration of ionized calcium depends on the integrated function of a number of specialized cells (e.g., parathyroid and certain kidney epithelial cells). We recently identified another G protein-coupled receptor (BoPCaR1) from bovine parathyroid that responds to changes in extracellular Ca2+ within the millimolar range and provides a key mechanism for regulating the secretion of parathyroid hormone. Using an homology-based strategy, we now report the isolation of a cDNA encoding an extracellular Ca2+/polyvalent cation-sensing receptor (RaKCaR) from rat kidney, The predicted RaKCaR protein shares 92% identity with BoPCaR1 receptor and features a seven membrane-spanning domain, characteristic of the G protein-coupled receptors, which is preceded by a large hydrophilic extracellular NH2 terminus believed to be involved in cation binding, RaKCaR cRNA-injected Xenopus oocytes responded to extracellular Ca2+, Mg2+, Gd3+, and neomycin with characteristic activation of inositol phospholipid-dependent, intracellular Ca2+-induced Cl- currents. In rat kidney, Northern analysis revealed RaKCaR transcripts of 4 and 7 kb, and in situ hybridization showed localization primarily in outer medulla and cortical medullary rays. Our results provide important insights into the molecular structure of an extracellular Ca2+/polyvalent cation-sensing receptor in rat kidney and provide another basis on which to understand the role of extracellular divalent cations in regulating kidney function in mineral metabolism.