Ni2+ impairs thrombin-induced signal transduction by acting on the agonist and/or receptor in human platelets.
We have investigated the effect of NiCl2 on platelet activation induced by thrombin, phorbol 12-myristate 13-acetate, and calcium ionophores. Besides blocking Ca2+ influx, NiCl2 inhibited platelet aggregation, intracellular Ca2+ mobilization, and phospholipase C activation induced by thrombin in a dose-dependent manner. In contrast to ionomycin, NiCl2 completely blocked the platelet aggregation and intracellular Ca2+ mobilization induced by A23187. A23187 was not able to translocate Ni2+ across the plasma membrane. Ni2+ also inhibited phorbol myristate acetate-induced platelet aggregation. The results with staurosporine and low NiCl2 concentrations are in agreement in that increases in intracellular Ca2+ concentration and protein kinase C activation are necessary for full platelet activation mediated by thrombin.
Azula
F J
FJ
Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Basque Country, Bilbao, Spain.
Alonso
R
R
Marino
A
A
Trueba
M
M
Macarulla
J M
JM
D000470:Alkaloids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D016257:Fura-2; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009532:Nickel / Q000097:blood / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood; D018179:Receptors, Thrombin / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000470:Alkaloids; D010975:Platelet Aggregation Inhibitors; D018179:Receptors, Thrombin; D000001:Calcimycin; C022838:nickel chloride; D009532:Nickel; D011493:Protein Kinase C; D013917:Thrombin; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016257:Fura-2