Inhibition of agonist-induced Ca2+ entry in endothelial cells by myosin light-chain kinase inhibitor.
Identification of the signal which links the depletion of Ca2+ stores to a Ca2+ entry pathway in the plasma membrane remains to be determined. In the present study, effects of ML-9 and wortmannin, inhibitors of myosin light-chain kinase (MLCK), on agonist-stimulated Ca2+ response were investigated in porcine aortic endothelial cells loaded with the Ca(2+)-sensitive dye fura-2. Bradykinin (BK) caused a rapid increase in [Ca2+]i, followed by a sustained increase due to the influx of Ca2+ from the extracellular space. ML-9 almost completely abolished the sustained increase in [Ca2+]i in BK-stimulated cells, while it did not affect the mobilization of Ca2+ from intracellular stores. ML-9 also abolished the sustained increase in [Ca2+]i caused by thapsigargin. Wortmannin mimicked the effect of ML-9 on the thapsigargin-stimulated Ca2+ response. These findings document for the first time the involvement of MLCK inhibitor in Ca2+ signaling in endothelial cells.
Watanabe
H
H
Hamamatsu University School of Medicine, Japan.
Takahashi
R
R
Zhang
X X
XX
Kakizawa
H
H
Hayashi
H
H
Ohno
R
R
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000032:analysis; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D009219:Myosin-Light-Chain Kinase / Q000032:analysis*; D015398:Signal Transduction; D013552:Swine; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D000077191:Wortmannin
D000730:Androstadienes; D001381:Azepines; D004791:Enzyme Inhibitors; D013729:Terpenes; C056218:ML 9; D019284:Thapsigargin; D009219:Myosin-Light-Chain Kinase; D000252:Calcium-Transporting ATPases; D001920:Bradykinin; D002118:Calcium; D000077191:Wortmannin