Exposure of platelet fibrinogen receptors by zinc ions: role of protein kinase C.
Previous studies demonstrated that Zn2+ at a concentration of 50 microM increases the number of fibrinogen receptors exposed on ADP-stimulated platelets and that higher concentrations of Zn2+ induce platelet aggregation that appears to be mediated by receptors associated with the glycoprotein IIb/IIIa complex. The purpose of this study was to identify the mechanism by which Zn2+ modulates exposure of fibrinogen receptors on the surface of human washed platelets. We determined that Zn2+ (300-800 microM)-induced platelet aggregation that was not accompanied by the release of [14C]serotonin was not blocked by ADP scavenging enzymes and 5'-p-fluorosulfonylbenzoyl-adenosine, an affinity label for ADP binding sites, but it was inhibited by disintegrins, staurosporine, and EDTA. Zn2+ (50-200 microM) showed a synergistic effect on platelet aggregation and platelet release caused by ADP and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, a Zn2+ chelator, and inhibited ADP-induced platelet aggregation that was reversed by Zn2+ (50 microM). Zn2+ (200 microM) increased the number of fibrinogen binding sites and the affinity of albolabrin (a disintegrin isolated from Trimeresurus albolabris snake venom that has been shown to bind to the fibrinogen receptor) on ADP-activated platelets. On the other hand, Zn2+ (100-800 microM) did not increase fibrinogen binding to the purified receptor. Incubation of platelets with Zn2+ (200 microM) resulted in the phosphorylation of a 47-kDa protein that was blocked by staurosporine, an inhibitor of protein kinase C. In conclusion, Zn2+ ions activate protein kinase C and enhance fibrinogen receptor exposure on the surface of platelets stimulated by ADP.
Trybulec
M
M
Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Kowalska
M A
MA
McLane
M A
MA
Silver
L
L
Lu
W
W
Niewiarowski
S
S
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005340:Fibrinogen / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D010750:Phosphoproteins / Q000097:blood / Q000302:isolation & purification; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D015032:Zinc / Q000097:blood / Q000494:pharmacology*
D000470:Alkaloids; D010750:Phosphoproteins; D010980:Platelet Membrane Glycoproteins; D014268:Trifluoperazine; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D011493:Protein Kinase C; D019311:Staurosporine; D015032:Zinc; D013755:Tetradecanoylphorbol Acetate