Zinc-induced platelet aggregation is mediated by the fibrinogen receptor and is not accompanied by release or by thromboxane synthesis.
We demonstrate that zinc (0.1 to 0.3 mmol/L) induces aggregation of washed platelet suspensions. Higher concentrations (1 to 3 mmol/L) of zinc were needed to aggregate platelets in platelet-rich plasma obtained from blood anticoagulated with low-molecular-weight heparin, probably due to the binding of zinc to the plasma proteins. Zinc-induced aggregation of normal washed platelets required added fibrinogen and no aggregation occurred with thrombasthenic platelets or with normal platelets pretreated with a monoclonal antibody (10E5) that blocks the platelet fibrinogen receptor. These data indicate that the platelet membrane fibrinogen receptor-glycoproteins IIb and IIIa mediate the effect of zinc. Zinc-induced aggregation was blocked by the agent TMB-8, which interferes with the internal calcium flux, and by prostacyclin, which elevates platelet cyclic adenosine monophosphate levels. Zinc-induced aggregation was not accompanied by thromboxane synthesis or by the secretion of dense-body serotonin and was not affected by preexposure of platelets to acetylsalicylic acid. Experiments with creatine phosphate/creatine phosphokinase showed that the zinc effect on platelets was independent of extracellular adenosine diphosphate (ADP). Zinc had an additive effect when platelet aggregation was stimulated with subthreshhold concentrations of collagen or ADP. Together with the known effects of nutritional zinc on in vivo bleeding, on platelet aggregation, and on lipid metabolism, the results suggest that zinc may have an important bearing on normal hemostasis, thrombosis, and atherosclerosis.
Heyns
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D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001791:Blood Platelet Disorders / Q000097:blood; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D003094:Collagen / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006023:Glycoproteins / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008345:Manganese / Q000097:blood; D008565:Membrane Proteins / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000502:physiology*; D012701:Serotonin / Q000097:blood; D013928:Thromboxane A2 / Q000097:blood*; D013931:Thromboxanes / Q000097:blood*; D015032:Zinc / Q000494:pharmacology*
D001095:Arachidonic Acids; D006023:Glycoproteins; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D013931:Thromboxanes; D016718:Arachidonic Acid; D012701:Serotonin; D008345:Manganese; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003300:Copper; D006493:Heparin; D003094:Collagen; D011464:Epoprostenol; D015032:Zinc; D002118:Calcium