Role of lipoxygenase metabolism in platelet function: effect of aspirin and salicylate.
Aspirin inhibits thromboxane A2 (TxA2) production whereas its salicylate moiety inhibits 12-hydroxy-eicosatetraenoic acid (12-HETE) production in the platelet. The significance of the latter effect on platelet function is unclear. We examined the effects of aspirin and salicylate on (i) platelet/collagen adhesion using 3H-adenine-labelled human platelets and collagen-coated discs, (ii) platelet aggregation induced by thrombin, collagen, ADP and arachidonic acid, and (iii) platelet TxA2 and 12-HETE synthesis as measured by radioimmunoassay and high pressure liquid chromatography respectively. Aspirin (50 uM) decreased platelet aggregation and increased platelet adhesion. The decrease in aggregation was associated with inhibition of TxA2 production and the increase in adhesion was associated with enhanced 12-HETE production. Salicylate had the opposite effects. Platelet aggregation was increased and platelet adhesion decreased. The increased aggregation was associated with enhanced TxA2 production and the decrease in aggregation was associated with inhibition of 12-HETE production. These observations suggest that 12-HETE facilitates platelet adhesion which can be altered by salicylate treatment.
Buchanan
M R
MR
Butt
R W
RW
Hirsh
J
J
Markham
B A
BA
Nazir
D J
DJ
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D008084:Lipoxygenase / Q000097:blood*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid; D013929:Thromboxane B2 / Q000096:biosynthesis
D006893:Hydroxyeicosatetraenoic Acids; D012459:Salicylates; D015117:5,8,11,14-Eicosatetraynoic Acid; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D003094:Collagen; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D020156:Salicylic Acid; D001241:Aspirin