Dioleoyl phosphatidic acid increases intracellular Ca2+ through endogenous LPA receptors in C6 glioma and L2071 fibroblasts
Dioleoyl phosphatidic acid increases intracellular Ca2+ through endogenous LPA receptors in C6 glioma and L2071 fibroblasts
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DOI：
10.1016/j.prostaglandins.2007.01.014
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发表时间：
2007-06-01
影响因子：
2.9
通讯作者：
Im, Dong-Soon
中科院分区：
文献类型：
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作者：
Chang, Young-Ja;Kim, Yu-Lee;Im, Dong-Soon
磷脂酸（PA）可增加C6大鼠胶质瘤细胞和L2071小鼠成纤维细胞内Ca ~（2+）浓度（[Ca ~（2+）]（i））。二油酰PA（PA，18：1）是最有效的，其次是二棕榈酰PA（16：0 PA）和二肉豆蔻酰PA（14：0 PA）。溶血磷脂酸（LPA）也可增加细胞内[Ca ~（2+）]（i）。PA对LPA诱导的C6细胞钙反应完全脱敏，但对L2071细胞部分脱敏。G（i/o）-型G蛋白的特异性抑制剂百日咳毒素（PTX）的处理完全改善了LPA和PA诱导的C6细胞中的Ca 2+反应。然而，在L2071细胞中，PTX抑制PA诱导的Ca 2+升高80%，抑制LPA诱导的Ca 2+升高20%。LPA（1）/LPA（3）受体特异性抑制剂Ki 16425可完全抑制LPA和PA诱导的C6细胞Ca ~（2+）反应。在L2071细胞中，Ki 16425完全抑制PA诱导的Ca ~（2+）反应，但部分抑制LPA诱导的Ca ~（2+）反应。另一种LPA（1）/LPA（3）受体特异性抑制剂VPC 32183可完全抑制LPA和PA诱导的C6和L2071细胞内Ca ~（2+）反应。因此，PA和LPA似乎通过与C6细胞中PTX敏感性G蛋白偶联的Ki 16425 NPC 32183敏感性LPA受体增加[Ca 2 +]（i）。然而，在L2071细胞中，LPA通过与PTX不敏感的G蛋白偶联的Kil 6425不敏感的LPA受体和与PTX敏感的G蛋白偶联的Kil 6425敏感的LPA受体增加[Ca 2 +]，而PA仅利用后一种途径。我们的研究结果表明，PA作为内源性LPA受体的部分激动剂，这是敏感的Ki 16425和耦合到PTX敏感的G蛋白，但不对LPA受体，这是不敏感的Ki 16425和耦合到PTX不敏感的G蛋白。(c)2007年爱思唯尔公司All rights reserved.
Phosphatidic acid (PA) increased intracellular Ca2+ concentration ([Ca2+](i)) in C6 rat glioma and L2071 mouse fibroblast cells. Dioleoyl PA (PA, 18: 1) was the most efficacious, followed by dipalmitoyl PA (16:0 PA) and dimyristoyl PA (14:0 PA). Lysophosphatidic acid (LPA) also increased the [Ca2+](i) in the both cells. PA desensitized LPA-induced Ca2+ response completely in C6 cells, but partly in L2071 cells. Treatment of pertussis toxin (PTX), a specific inhibitor of G(i/o)-type G proteins, completely ameliorated LPA- and PA-induced Ca2+ response in C6 cells. However, in L2071 cells, PTX inhibited PA-induced Ca2+, increase by 80% and LPA-induced one by 20%. Ki 16425, a specific inhibitor of LPA(1)/LPA(3) receptors, completely inhibited both LPA- and PA-induced Ca2+ responses in C6 cells. On the other hand, in L2071 cells, Ki 16425 completely inhibited PA-induced Ca2+ response, but partly LPA-induced one. VPC32183, another specific inhibitor of LPA(1)/LPA(3) receptors, completely inhibited LPA- and PA-induced Ca2+ responses in both C6 and L2071 cells. Therefore, PA and LPA appear to increase [Ca2+](i) through Ki16425NPC32183-sensitive LPA receptor coupled to PTX-sensitive G proteins in C6 cells. In L2071 cells, however, LPA increases [Ca2+], through Kil6425-insensitive LPA receptor coupled to PTX-insensitive G proteins and Kil6425-sensitive LPA receptor coupled to PTX-sensitive G protein, whereas PA utilized only the latter pathway. Our results suggest that PA acts as a partial agonist on endogenous LPA receptors, which are sensitive to Ki 16425 and coupled to PTX-sensitive G protein, but not on LPA receptors, which are not sensitive to Ki 16425 and coupled to PTX-insensitive G protein. (c) 2007 Elsevier Inc. All rights reserved.