Second messenger function of phosphatidic acid in platelet activation.
Phosphatidic acid (PA) is synthesized as the result of the receptor-mediated response of platelets to physiologic agonists. The role of PA in platelet signal transduction, however, is largely unknown. We have examined the responses of platelets to 1-stearoyl-2-arachidonoyl phosphatidic acid (SAPA), the predominant molecular species of human platelet PA. SAPA alone causes platelet aggregation, and pretreatment of platelets with SAPA markedly enhances thrombin-induced aggregation and secretion. Addition of SAPA to intact human platelets causes rapid breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) and the generation of diacylglycerol and endogenous PA. These reactions are associated with mobilization of intracellular calcium and activation of protein kinase C. SAPA also stimulates the release of endogenous arachidonic acid and its conversion to thromboxane A2. Furthermore, platelet activation by SAPA is blocked by indomethacin, indicating that the actions of SAPA are mediated by cyclooxygenase products. These findings suggest that SAPA may play an important role as an endogenous positive feedback signal to amplify receptor-mediated activation of PIP2-specific phospholipase C in human platelets.
Kroll
M H
MH
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Zavoico
G B
GB
Schafer
A I
AI
D000255:Adenosine Triphosphate / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000097:blood; D006801:Humans; D008055:Lipids / Q000097:blood; D010712:Phosphatidic Acids / Q000097:blood* / Q000494:pharmacology / Q000502:physiology; D010766:Phosphorylation; D010974:Platelet Aggregation; D015290:Second Messenger Systems; D013928:Thromboxane A2 / Q000097:blood
D001798:Blood Proteins; D008055:Lipids; D010712:Phosphatidic Acids; C060203:1-stearoyl-2-arachidonoylphosphatidic acid; D013928:Thromboxane A2; D000255:Adenosine Triphosphate; D002118:Calcium