Carrageenan-induced activation of human platelets is independent of phospholipase A2 and of formation of thromboxanes.
Aggregation of washed rabbit platelets by thrombin and by carrageenan is accompanied by the activation of phospholipase A2 and by the synthesis of thromboxanes. Accordingly, aggregation, the accompanying release reaction and the activation of phospholipase are blocked by p-bromophenacyl bromide and by CB 874 (2,3-dibromo (4'-cyclohexyl-3'-chloro)-phenyl-4-oxo-butyric acid), two recognized inhibitors of the enzyme. Since these two reagents also inhibit aggregation and the release reaction induced by thrombin and by carrageenan on washed human platelets, it might have been anticipated that the mechanisms of aggregation of the platelets from the two species are similar. Nevertheless, no thromboxanes A2 or B2, nor activation of phospholipase A2 could be demonstrated with the use of carrageenan on human platelets, under conditions where thrombin was effective. It is concluded that carrageenan activates the human platelets by phospholipase A2- and thromboxane A2-independent mechanisms, and that the inhibitors of phospholipase A2 may block platelet functions by mechanisms other than inhibition of the expected enzyme.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002351:Carrageenan / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D010105:Oxygenases / Q000502:physiology; D010740:Phospholipases / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D054467:Phospholipases A2; D010974:Platelet Aggregation / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis*
D013931:Thromboxanes; D000244:Adenosine Diphosphate; D002351:Carrageenan; D010105:Oxygenases; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin