Inhibition by antioxidants of agonist evoked cytosolic Ca++ increase, ATP secretion and aggregation of aspirinated human platelets.
The synthetic antioxidants butylated hydroxytoluene (BHT), nordihydroguaiaretic acid and the one-electron donor 1,1'-dimethylferrocene, inhibit cytosolic Ca++ increase, shape change, aggregation and ATP secretion in aspirinated washed human platelets stimulated by thrombin, vasopressin and platelet-activating factor. The antioxidants also inhibit cytosolic Ca++ increase originating from intracellular stores in the presence of EGTA. The effect of phorbol ester (TPA), which promotes platelet aggregation and secretion without raising the cytosolic Ca++, is also antioxidant-sensitive. Since agonist activation of aspirinated platelets does not involve cyclooxygenase or lipoxygenase metabolites, it is suggested that other yet unknown free radical-dependent pathways are involved in the mechanism of platelet activation, both in the protein kinase C-independent events leading to the cytosolic Ca++ increase, and in those, largely protein kinase C-dependent, leading to aggregation and ATP secretion.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D009637:Masoprocol / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D000975:Antioxidants; D005296:Ferrous Compounds; D009942:Organometallic Compounds; D010972:Platelet Activating Factor; D014667:Vasopressins; C050099:1,1'-dimethylferrocene; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; D004533:Egtazic Acid; D009637:Masoprocol; D000255:Adenosine Triphosphate; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D001241:Aspirin; D002118:Calcium