REGULATION OF BRADYKININ-STIMULATED CATION ENTRY INTO ENDOTHELIAL-CELLS BY TYROSINE KINASE

In endothelial cells, bradykinin stimulates the release of intracellul ar Ca2+, which is followed by the entry of extracellular Ca2+ into the cells. However, the mechanism underlying this Ca2+ entry is not well understood. To investigate the possible implication of tyrosine kinase s 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 inhibit ors genistein and herbimycin A attenuated not only Ca2+ influx but als o Mn2+ influx from the extracellular space without affecting the relea se of Ca2+ from internal stores in bradykinin-treated cells. In contra st to tyrosine kinase inhibitors, the tyrosine phosphatase inhibitor v anadate stimulated Ca2+ influx as weil as Mn2+ influx. On the other ha nd, both an inactive analog of genistein, daidzein, and an inhibitor o f diacylglycerol (DAG) kinase, ethylene glycol dioctanoate, were witho ut effect on [Ca2+](i) following the stimulation of agonist. These fin dings suggest that tyrosine kinase is involved in the regulation of ca tion influx in endothelial cells.