Regulation of bradykinin-stimulated cation entry into endothelial cells by tyrosine kinase.
In endothelial cells, bradykinin stimulates the release of intracellular Ca2+, which is followed by the entry of extracellular Ca2+ into the cells. However, the mechanism underlying the Ca2+ entry is not well understood. To investigate the possible implication of tyrosine kinases in bradykinin-mediated Ca2+ signaling in endothelial cells, cultured porcine aortic endothelial cells were loaded with fura-2/AM, and Mn2+ influx into the cells was determined by the quenching of fluorescence intensity of fura-2 at 360 nm excitation. The tyrosine kinase inhibitors genistein and herbimycin A attenuated not only Ca2+ influx but also Mn2+ influx from the extracellular space without affecting the release of Ca2+ from internal stores in bradykinin-treated cells. In contrast to tyrosine kinase inhibitors, the tyrosine phosphatase inhibitor vanadate stimulated Ca2+ influx as well as Mn2+ influx. On the other hand, both an inactive analog of genistein, daidzein, and an inhibitor of diacylglycerol (DAG) kinase, ethylene glycol dioctanoate, were without effect on [Ca2+]i following the stimulation of agonist. These findings suggest that tyrosine kinase is involved in the regulation of cation influx in endothelial cells.
Takahashi
R
R
Department of Internal Medicine III, Hamamatsu University School of Medicine, Japan.
Watanabe
H
H
Kakizawa
H
H
Zhang
X X
XX
Hayashi
H
H
Ohno
R
R
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine
D011505:Protein-Tyrosine Kinases; D001920:Bradykinin; D002118:Calcium