Sensitizing effect of lysophosphatidic acid on Ca2+ response to hypotonic stress in cultured lens epithelial cells

The effects of lysophosphatidic acid (LPA), a bioactive phospholipid, on th e response of the cytosolic free Ca2+ concentration ([Ca2+](i)) to hypotoni c stress were studied in cultured bovine lens epithelial cells, to test whe ther LPA affects cellular swelling-mediated increase in [Ca2+](i), which ma y relate to formation of sugar cataracts. Exposure of the cells to a 30% hy potonic stress caused only a slight increase in [Ca2+](i). Pretreatment wit h LPA (10 mu M) significantly augmented the hypotonic stress-induced [Ca2+] (i) response, whereas addition of LPA to the cells did not affect [Ca2+](i) . The hypotonic stress-induced increase in [Ca2+](i) in the presence of LPA was inhibited by Gd3+, a blocker of mechanosensitive cation channels, but not by nicardipine, a L-type Ca2+ channel blocker, or thapsigargin, an inhi bitor of endoplasmic reticulum-ATPase pump. These results show that LPA sen sitizes the response to hypotonic stress via increase in Ca2+ influx throug h Gd3+-sensitive stretch-activated ion channels, and not via Ca2+ release f rom intracellular stores. On the other hand, LPA did not affect the [Ca2+]( i) response to ATP, a Ca2+ mobilizing agonist. Therefore, LPA sensitizes th e hypotortic stress-induced [Ca2+](i) response in lens epithelial cells, su ggesting that LPA potentiates the development of cataracts induced by cellu lar swelling such as sugar cataract.