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 the response of the cytosolic free Ca2+ concentration ([Ca2+]i) to hypotonic stress were studied in cultured bovine lens epithelial cells, to test whether LPA affects cellular swelling-mediated increase in [Ca2+]i, which may relate to formation of sugar cataracts. Exposure of the cells to a 30% hypotonic stress caused only a slight increase in [Ca2+]i. Pretreatment with LPA (10 microM) 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 inhibitor of endoplasmic reticulum-ATPase pump. These results show that LPA sensitizes the response to hypotonic stress via increase in Ca2+ influx through Gd3+-sensitive stretch-activated ion channels, and not via Ca2+ release from intracellular stores. On the other hand, LPA did not affect the [Ca2+]i response to ATP, a Ca2+ mobilizing agonist. Therefore, LPA sensitizes the hypotonic stress-induced [Ca2+]i response in lens epithelial cells, suggesting that LPA potentiates the development of cataracts induced by cellular swelling such as sugar cataract.
Ohata
H
H
Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan. ohata@pharm.showa-u.ac.jp
Tanaka
K
K
Momose
K
K
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D007038:Hypotonic Solutions; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D003470:Culture Media; D004791:Enzyme Inhibitors; D007038:Hypotonic Solutions; D008246:Lysophospholipids; D019284:Thapsigargin; D005682:Gadolinium; D009529:Nicardipine; D000251:Adenosine Triphosphatases; D002118:Calcium