Primary role of calcium ions in arachidonic acid release from rat platelet membranes. Comparison with human platelet membranes.

The liberation of arachidonic acid (AA) was investigated in platelet membranes prelabelled with 3H]AA. In rat platelet membranes, Ca2+ at concentrations over several hundred nanomolar induced 3H]AA release, with a concurrent decrease in 3H radioactivity of phosphatidylethanolamine and phosphatidylcholine. Some 4-6% of total radioactivity incorporated into platelet membrane lipids was released at 1-10 microM-Ca2+, which is nearly equivalent to that attained in agonist-stimulated platelets. Formation of lysophospholipids in 3H]glycerol-labelled membranes and decrease in 3H]AA liberated by the phospholipase A2 inhibitors mepacrine and ONO-RS-082 suggest that 3H]AA release is mainly catalysed by phospholipase A2. In intact platelets agonist-stimulated 3H]AA release was markedly decreased in the absence of extracellular Ca2+ or in the presence of the intracellular Ca2+ chelator quin 2. These results indicate that in rat platelets the rise of intracellular Ca2+ plays a primary role in the activation of phospholipase A2. In contrast, Ca2+ even at high millimolar concentrations did not effectively stimulate 3H]AA release in human platelet membranes. Thus factor(s) additional to or independent of Ca2+ is required for the liberation of AA in human platelets.