THE MECHANISM OF ARACHIDONIC-ACID RELEASE IN COLLAGEN-ACTIVATED HUMAN PLATELETS

The mechanism of arachidonic acid (AA) release in collagen-activated human platelets was studied. An arachidonic acid metabolite, thromboxane B-2 (TXB(2)), was formed in parallel with the formation of phosphatidic acid (PA) without formation of lysophosphatidic acid (lysoPA) or lysophosphatidylinositol (lysoPI) in the absence of extracellular Ca2+, suggesting that AA was released from PI via a PI-specific phospholipase C (PI-PLC)/diacylglycerol (DG) lipase/monoacylglycerol (MG) Lipase pathway under the cytosolic low Ca2+ concentrations. Moreover, solubilized DG lipase and MG lipase could hydrolyze the substrates at basal cytosolic free Ca2+ concentrations. Subsequently, the relationship of cytosolic free Ca2+ concentrations and formation of AA metabolites was analyzed using Ca2+ ionophore, A23187. Collagen was able to induce a release of small amounts of AA under basal cytosolic Ca2+ conditions. However, a release of large amounts of AA was induced by phospholipase A(2) activated by both collagen-receptor occupancy and elevated Ca2+ levels. A TXA(2) mimetic agonist, STA(2) induced all the responses except for AA release. From these results, the mechanism of AA release and signal transduction in collagen-activated human platelets is discussed.