In endothelial cells, bradykinin stimulates the release of intracellular Ca
2+, which is followed by the entry of extracellular Ca
2+ into the cells. However, the mechanism underlying this Ca
2+ entry is not well understood. To investigate the possible implication of tyrosine kinases in bradykinin-mediated Ca
2+ signaling in endothelial cells, cultured porcine aortic endothelial cells were loaded with fura-2/AM, and Mn
2+ 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 Ca
2+ influx but also Mn
2+ influx from the extracellular space without affecting the release of Ca
2+ from internal stores in bradykinin-treated cells. In contrast to tyrosine kinase inhibitors, the tyrosine phosphatase inhibitor vanadate stimulated Ca
2+ influx as well as Mn
2+ 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 [Ca
2+]
i following the stimulation of agonist. These findings suggest that tyrosine kinase is involved in the regulation of cation influx in endothelial cells. (
Jpn Circ J 1997;
61: 1030 - 1036)
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