Lysophosphatidic acid sensitizes mechanical stress-induced Ca 2+ mobilization in cultured human lung epithelial cells

Abstract

We conformed that lysophosphatidic acid (LPA), which is known to be released from activated platelets, sensitizes response in cytosolic free Ca 2+ concentration ([Ca 2+] i) to mechanical stimulation in cultured epithelial cells (REPF-LC-AI cells) from human lung carcinoma. [Ca 2+] i was transiently increased by spritzing of bath solution onto cells as mechanical stimulation in the presence of LPA with concentration-dependent manner (10–100nM). The transient increase induced by the mechanical stimulation in the presence of LPA was inhibited by 10 μM Ga 3+ or removing extracellular Ca 2+, but not by 10 μM nicaridipine, suggesting that LPA sensitizes mechanical stimulation-induced Ca 2+ influx through stretch-activated ion channels. Phosphatidic acid (1 μM), but not lysophosphatidycholine (10 μM), 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.