Platelet activation by tetraprenol via stimulation of phospholipase A2 action.
Only tetraprenol (n = 4), among the (n)-polyprenols studied, induced activation of rabbit platelets. Tetraprenol-induced responses, including platelet aggregation, Ca2+ mobilization, inositol phosphate formation, and arachidonic acid release, were greatly inhibited by a thromboxane A2 (TXA2) receptor antagonist and a cyclooxygenase inhibitor, indicating an essential role for endogenously produced TXA2. The TXA2-mimetic agonist U46619 induced platelet aggregation, Ca2+ mobilization and phospholipase C action but did not induce arachidonic acid release. These results suggest that arachidonic acid is not released via phospholipase C but by phospholipase A2, and this is also supported by the finding that phospholipase C action was inhibited by depletion of extracellular Ca2+, while arachidonic acid release was not. Full arachidonic acid release was found to be induced by the synergistic action of U46619 and tetraprenol. Therefore, the initial, most essential response induced by tetraprenol is a small arachidonic acid release by phospholipase A2, which results in initial TXA2 formation. Further action of phospholipase C as well as Ca2+ mobilization and aggregation were induced by the initially formed TXA2 while further activation of phospholipase A2 required the synergistic action of tetraprenol and TXA2.
Nakano
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka.
Matsumoto
S
S
Hanasaki
K
K
Arita
H
H
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D002118:Calcium / Q000097:blood; D004224:Diterpenes / Q000494:pharmacology*; D004357:Drug Synergism; D006868:Hydrolysis; D066298:In Vitro Techniques; D008055:Lipids / Q000097:blood; D010740:Phospholipases / Q000097:blood*; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D013729:Terpenes / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000502:physiology
D001095:Arachidonic Acids; D004224:Diterpenes; D008055:Lipids; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013729:Terpenes; D016718:Arachidonic Acid; D013928:Thromboxane A2; C017338:geranylgeraniol; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium