Lanthanum activates calcium-sensing receptor and enhances sensitivity to calcium
Lanthanum activates calcium-sensing receptor and enhances sensitivity to calcium
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DOI：
10.1093/ndt/gfq124
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发表时间：
2010-09-01
影响因子：
6.1
通讯作者：
Benito Cannata-Andia, Jorge
中科院分区：
文献类型：
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作者：
Carrillo-Lopez, Natalia;Luis Fernandez-Martin, Jose;Benito Cannata-Andia, Jorge
背景本研究的目的是调查是否纳摩尔浓度的镧可以影响钙敏感受体（CaSR）的反应。用人CaSR瞬时转染的胚胎肾（HEK-293）细胞用于测试镧单独或与钙联合激活CaSR的能力。通过流式细胞术测量CaSR活化。取肾功能正常的4月龄雄性Wistar大鼠（n = 60）的甲状旁腺，用不同浓度的镧进行体外培养，测定甲状旁腺激素（PTH）分泌量和PTH mRNA。由11 μ M氯化镧（LaCl 3）诱导的最大CaSR活化与由16 mM氯化钙诱导的最大CaSR活化相似（CaCl 2 16 mM：294 +/- 14%; LaCl 3 1 μ M：303 +/- 11%）。镧的半有效浓度（EC 50）为77.28 nM，低于钙的2.30 mM，支持这种金属是CaSR的强激动剂的概念。此外，镧还能够增强CaSR对钙的敏感性。1 nM LaCl 3的存在使CaSR响应曲线显著左移，将钙的EC 50值从2.30 mM（单独钙）变为1.26 mM（钙+ 1 nM镧）。与对照腺体相比，用镧培养的甲状旁腺显示出分泌较少PTH的趋势：1.51 +/- 0.23（对照）、0.91 +/- 0.17（La 100 nM）和1.04 +/- 0.18（La 400 nM）[（pg/h）/（pg/h），平均值+/- SEMI（ANOVA P = 0.0145）。通过PTH mRNA水平测定的PTH合成也观察到类似的趋势。这些体外研究结果表明，镧，在纳摩尔浓度，是一种激动剂的CaSR能够激活它在没有钙。此外，它还可以增强CaSR对钙的敏感性，调节PTH的合成和分泌。
Background. The aim of this study was to investigate whether nanomolar concentrations of lanthanum could influence the calcium-sensing receptor (CaSR) response.Methods. Embryonic kidney (HEK-293) cells transiently transfected with the human CaSR were used to test the ability of lanthanum to activate the CaSR, either alone or in combination with calcium. CaSR activation was measured by flow cytometry. Parathyroid glands from 4-month-old male Wistar rats with normal renal function (n = 60) were also cultured ex vivo with different concentrations of lanthanum to measure parathyroid hormone (PTH) secreted to the medium and PTH mRNA.Results. The maximal CaSR activation induced by 1 1 mu M lanthanum chloride (LaCl3) was similar to that induced by 16 mM calcium chloride (CaCl2 16 mM: 294 +/- 14%; LaCl3 1 mu M: 303 +/- 11%). Lanthanum half effective concentration (EC50) was 77.28 nM, lower than the 2.30 mM obtained for calcium, supporting the concept that this metal is a strong agonist of the CaSR. Moreover, lanthanum was also able to enhance CaSR sensitivity to calcium. The presence of 1 nM LaCl3 significantly left-shifted the CaSR response curve, changing the EC50 value for calcium from 2.30 mM (calcium alone) to 1.26 mM (calcium + 1 nM lanthanum). The parathyroid glands cultured with lanthanum showed a trend to secrete less PTH compared to the control glands: 1.51 +/- 0.23 (control), 0.91 +/- 0.17 (La 100 nM) and 1.04 +/- 0.18 (La 400 nM) [(pg/h)/(pg/h), mean +/- SEMI (ANOVA P = 0.0145). A similar trend was also observed in PTH synthesis measured by PTH mRNA levels.Conclusions. These in vitro findings demonstrate that lanthanum, at nanomolar concentrations, is an agonist of the CaSR able to activate it in the absence of calcium. In addition, it can also enhance CaSR sensitivity to calcium, modulating PTH synthesis and secretion.