Roles of inhibitors of myosin light chain kinase and tyrosine kinase on cation influx in agonist-stimulated endothelial cells.
Agonist-stimulated Ca2+ influx is critically important to mediate the function of endothelial cells. It has been suggested that release of Ca2+ from internal stores activates Ca2+ influx across the plasma membrane. In the present study, we investigated the effects of ML-9, a myosin light-chain kinase (MLCK) inhibitor, and genistein, a tyrosine kinase inhibitor, on the agonist stimulated Ca2+ response in porcine aortic endothelial cells loaded with a Ca2+-sensitive dye, fura-2. ML-9 almost completely abolished Ca2+ influx, whereas genistein only partially attenuated Ca2+ entry. Both of them did not affect the mobilization of Ca2+ from internal stores. In contrast, genistein was more potent in the inhibition of Mn2+ influx than ML-9. These findings indicate the different selectivity for Ca2+ and Mn2+ in the cation entry pathway in agonist-stimulated endothelial cells.
Takahashi
R
R
Internal Medicine III, Hamamatsu University School of Medicine, Handa-cho, Japan. reikot1@hama-med.ac.jp
Watanabe
H
H
Zhang
X X
XX
Kakizawa
H
H
Hayashi
H
H
Ohno
R
R
D000818:Animals; D001011:Aorta; D001381:Azepines / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology*; D007700:Kinetics; D008345:Manganese / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013552:Swine; D019284:Thapsigargin / Q000494:pharmacology
D001381:Azepines; D002413:Cations, Divalent; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007529:Isoflavones; C049925:fura-2-am; C056218:ML 9; D008345:Manganese; D019284:Thapsigargin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D009219:Myosin-Light-Chain Kinase; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2