Cytochalasins inhibit arachidonic acid metabolism in thrombin-stimulated platelets.

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Abstract
Low concentrations (0.5-1 .mu.M) of cytochalasins inhibit the thrombin-stimulated polymerization of monomeric actin to filamentous actin in platelets. Similar concentrations of cytochalasin B inhibit the formation and metabolism of arachidonic acid in horse platelets stimulated by low concentrations of thrombin (0.1-0.5 U/ml). The release of serotonin is not inhibited by cytochalasin B. Cytochalasins B and D (0.5-1 .mu.M) markedly reduce, in thrombin-stimulated human or horse platelets, the metabolism of the liberated arachidonic acid by cyclooxygenase activity to thromboxane B2 and 12-hydroxy-5,8,10-hepatadecatrienoic acid and the conversion of arachidonic acid by lipoxygenase activity to 12-hydroxy-5,8,10,14-icosatetraenoic acid. The generation of arachidonic acid from platelet phospholipids and the formation of phosphatidic acid are much less affected by cytochalasin B or D. Cytochalasins do not directly inhibit platelet cyclooxygenase, lipoxygenase, phospholipase A2 or phosphatidylinositol-specific phospholipase C. The metabolism of exogenously added arachidonic acid by intact platelets is not inhibited by cytochalasins B and D. Polymerization of actin in platelets stimulated by thrombin may be required for the effective metabolism of arachidonic acid released from platelet phospholipids.