Metabolic responses induced by thrombin in human umbilical vein endothelial cells.
Metabolic responses induced by thrombin in human umbilical vein endothelial cells (HUVECs) were investigated by using the cytosensor technique. Thrombin increased the extracellular acidification rate of endothelial cells, measured as an index of metabolic activity with a cytosensor microphysiometer, in a concentration-dependent fashion with an EC(50) of 1.27+/-0.59 IU/ml, which was abolished by the MAP kinase inhibitor PD98059. When intracellular Ca(2+) was chelated or PKC was inactivated, PD98059 failed to abolish the thrombin-induced acidification rate response in HUVECs. In addition, the tyrosine kinase inhibitor genistein, PKC inhibitor calphostin C, and Na(+)/H(+)exchanger antagonist MIA also partly inhibited thrombin-induced acidification rate responses. It is suggested that thrombin stimulated rapid metabolic responses via MAP kinase in HUVECs, which are calcium- and PKC-dependent.
Fan
Yi
Y
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, People's Republic of China.
Wu
Da-Zheng
DZ
Gong
Yan-Qing
YQ
Xu
Ren
R
Hu
Zhi-Bi
ZB
D020013:Calcium Signaling; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*
D017923:Sodium-Hydrogen Exchangers; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D013917:Thrombin