It is known that stimulation of platelets with physiological agents such as arachidonic acid (AA) induces rapid changes in membrane phospholipids via the activation of the phosphatidylinositol (PI) pathway. This study indicates the role of thromboxane (TX) A2 in the changes in phospholipids in 3H-AA- or 3H-glycerol-labeled rabbit platelets using OKY-046, a specific TXA2 synthetase inhibitor, and 9, 11-epithio-11, 12-methano-TXA2 (STA2).
Stimulation of platelets with 0.5mM AA induced breakdown of 3H-PI and formation of 3H-1, 2-diacylglycerol, 3H-phosphatidic acid (PA) and 3H-AA in platelets. OKY-046 (10-6-10-4M) dose-dependently inhibited these changes in phospholipids, especially PA formation, 3min after the addition of AA. Aspirin (10-3M) also inhibited the changes in phospholipids. OKY-046 and aspirin also inhibited the changes after 5min induced by collagen (20μg/ml), however no effect was observed on the changes induced by 20μM ADP. On the other hand STA2, a TXA2 analogue, dose-dependently stimulated the formation of PA alone.
These results suggest that TXA2 stimulates platelets through the activation of membrane phospholipid metabolism such as PA formation via the PI pathway.