Cytochalasins inhibit arachidonic acid metabolism in thrombin-stimulated platelets.
Low concentrations (0.5-1 microM) 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 unit/ml). However, the release of serotonin is not inhibited by cytochalasin B. Cytochalasins B and D (0.5-1 microM) 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-heptadecatrienoic 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 phosphatidyl-inositol-specific phospholipase C. In addition, the metabolism of exogenously added arachidonic acid by intact platelets is not inhibited by cytochalasins B and D. The results indicate that polymerization of actin in platelets stimulated by thrombin may be required for the effective metabolism of arachidonic acid released from platelet phospholipids.
D000199:Actins / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003572:Cytochalasins / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D006736:Horses; D010740:Phospholipases / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D000199:Actins; D001095:Arachidonic Acids; D003572:Cytochalasins; D010740:Phospholipases; D013917:Thrombin