L-Amino acid sensing by the extracellular Ca2+-sensing receptor
L-Amino acid sensing by the extracellular Ca2+-sensing receptor
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DOI：
10.1073/pnas.97.9.4814
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发表时间：
2000-04-25
影响因子：
11.1
通讯作者：
Brown, EM
中科院分区：
文献类型：
--
作者：
Conigrave, AD;Quinn, SJ;Brown, EM
细胞外钙（Ca-o（2+））敏感受体（CaR）识别并响应（即，在本研究中，我们证明了CaR不仅被胞外钙离子激活，而且被氨基酸激活，建立了其感知两种完全不同类别的营养物质的能力，L-氨基酸，特别是芳香族氨基酸，包括L-苯丙氨酸和L-色氨酸，在CaR激动剂存在下立体选择性地移动Ca 2+离子，在用人CaR稳定转染的负载fura-2的人胚肾（HEK-293）细胞中的Ca-o（2+）、钆（Gd-o（3+））和精胺。L-氨基酸依赖性的影响，观察到以上，但不低于，阈值水平的Ca-O（2+）的约1.0 mM。L-氨基酸，特别是芳香族氨基酸，也立体选择性增强的敏感性的钙受体，其激动剂，Ca-O（2+）和精胺。支链氨基酸几乎没有活性，而带电氨基酸，包括精氨酸和赖氨酸，比芳香族和其他氨基酸的效果要差得多。模拟空腹人血浆氨基酸组成的L-氨基酸混合物再现了高浓度单独L-氨基酸对Ca 2+动员的作用，并增强了CaR对Ca-o（2+）的敏感性。本文提供的数据将CaR鉴定为芳香族和其他L-氨基酸的分子靶标。因此，CaR可以整合来自不同类别营养素的信号：矿物质离子和氨基酸。L-氨基酸对钙受体的作用可能为几种长期公认但知之甚少的膳食蛋白质对钙代谢的作用提供解释。
The extracellular calcium (Ca-o(2+))-sensing receptor (CaR) recognizes and responds to (i.e., "senses") Ca-o(2+) as its principal physiological ligand, In the present studies, we document that the CaR is activated not only by extracellular calcium ions but also by amino acids, establishing its capacity to sense nutrients of two totally different classes, L-Amino acids, especially aromatic amino acids, including L-phenylalanine and L-tryptophan, stereoselectively mobilized Ca2+ ions in the presence of the CaR agonists, Ca-o(2+), gadolinium (Gd-o(3+)), and spermine in fura-2-loaded human embryonic kidney (HEK-293) cells stably transfected with the human CaR. L-amino acid-dependent effects were observed above, but not below, a threshold level of Ca-o(2+) of approximately 1.0 mM. L-Amino acids, particularly aromatic amino acids, also stereoselectively enhanced the sensitivity of the CaR to its agonists, Ca-o(2+) and spermine. Branched-chain amino acids were almost inactive, and charged amino acids, including arginine and lysine, were much less effective than aromatic and other amino acids. L-amino acid mixtures emulating the amino acid composition of fasting human plasma reproduced the effects of high concentrations of individual L-amino acids on Ca2+ mobilization and enhanced the sensitivity of the CaR to Ca-o(2+). The data presented herein identify the CaR as a molecular target for aromatic and other L-amino acids. Thus, the CaR can integrate signals arising from distinct classes of nutrients: mineral ions and amino acids. The actions of L-amino acids on the CaR may provide explanations for several long recognized but poorly understood actions of dietary protein on calcium metabolism.