Ohata H, Seito N, Yoshida K, Momose K
Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Life Sci. 1996;58(1):29-36. doi: 10.1016/0024-3205(95)02252-x.
We conformed that lysophosphatidic acid (LPA), which is known to be released from activated platelets, sensitizes response in cytosolic free Ca2+ concentration ([Ca2+]i) to mechanical stimulation in cultured epithelial cells (REPF-LC-AI cells) from human lung carcinoma. [Ca2+]i was transiently increased by spritzing of bath solution onto cells as mechanical stimulation in the presence of LPA with concentration-dependent manner (10-100 nM). The transient increase induced by the mechanical stimulation in the presence of LPA was inhibited by 10 microM Ga3+ or removing extracellular Ca2+, but not by 10 microM nicaridipine, suggesting that LPA sensitizes mechanical stimulation-induced Ca2+ influx through stretch-activated ion channels. Phosphatidic acid (1 microM), but not lysophosphatidycholine (10 microM), histamine (100 nM), bradykinin (10 nM), nor ionomycin (100 nM), caused the same effect as that of LPA. This effect was observed in confluent cells, but not in subconfluent cells. These results show that LPA sensitizes mechanoreceptor-linked response in human lung epithelial cells, suggesting a possibility that LPA affects lung function, in particular, during pathological state.
我们证实，已知从活化血小板释放的溶血磷脂酸（LPA）可使来自人肺癌的培养上皮细胞（REPF-LC-AI细胞）中细胞溶质游离Ca2+浓度（[Ca2+]i）对机械刺激的反应敏感。在存在LPA（浓度为10 - 100 nM，呈浓度依赖性）的情况下，通过向细胞喷射浴液作为机械刺激，[Ca2+]i会短暂增加。在存在LPA的情况下，机械刺激诱导的短暂增加可被10 microM Ga3+或去除细胞外Ca2+抑制，但不能被10 microM尼卡地平抑制，这表明LPA通过拉伸激活离子通道使机械刺激诱导的Ca2+内流敏感。磷脂酸（1 microM）而非溶血磷脂胆碱（10 microM）、组胺（100 nM）、缓激肽（10 nM）或离子霉素（100 nM）产生与LPA相同的效果。这种效果在汇合细胞中观察到，但在亚汇合细胞中未观察到。这些结果表明，LPA可使人肺上皮细胞中的机械感受器相关反应敏感，提示LPA可能影响肺功能，特别是在病理状态下。
