Preferential Activation of Phospholipase A2, by Low Concentrations of Phosphatidic Acid with Long-Chain Fatty Acids in Rabbit Platelets1

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Abstract
The role of phosphatidic acid (PA) in the signal transduction system of platelets was studied using 1-stearoyl 2-arachidonoyl PA (PASA). When PASA was added to rabbit platelets, aggregation occurred. BW755C, a dual inhibitor of cyclooxygenase and lipoxygenase, as well as p-bromophenacyl bromide and mepacrine, inhibitors of phospholipase A2, inhibited the aggregation induced by low concentrations of PASA, but not that induced by high concentrations. PASA, also stimulated, in a dose-dependent manner, arachidonic acid liberation, lysophosphatidylcholine and diacylglycerol formation, and mobilization of intracellular Ca2Plus;; all of which were dependent on the presence of Ca2+ in the outer medium. The arachidonic acid liberation was inhibited by p-bromophenacyl bromide or mepacrine, while diacylglycerol formation by low concentrations of PASA, was inhibited by BW755C. With platelet membrane fractions or with the platelets made permeable to Ca2+ by pretreatment with ionomycin, PASA, caused arachidonic acid liberation in the presence of Ca2+. Furthermore, PASA, enhanced the activity of phospholipase A2, partially purified from platelet cytosol acting on 1-palmitoyl-2-[14C]arachidonoyl-glycerophosphoethanolamine. These results provide evidence that PASA, preferentially potentiates the activation of phospholipase A2, in cooperation with Ca2+, suggesting that PA acts as a positive feedback regulator to potentiate the activation of phospholipase A2, and contributes to the amplification of platelet activation.

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