Activation of human platelets by lysophosphatidic acid

The biochemical mechanisms of platelet activation by lysophosphatidic acid were investigated. Lysophosphatidic acid interacts with a membrane receptor coupled to the inhibitory GTP-binding protein Gi and produces a rapid decrease of the intracellular concentration of cAMP. Aggregation of gel-filtered platelets by lysophosphatidic acid requires the presence of extracellular CaCl₂, as this phospholipid does not induce secretion of platelet dense granules. Platelet activation by lysophosphatidic acid in the absence of extracellular CaCl₂ does not involve phospholipase C activation, Is evaluated by measuring mobilization of Ca²⁺ from internal stores and pleckstrin phosphorylation, but causes the rapid tyrosine phosphorylation of several intracellular proteins. Our results indicate that activation of intracellular tyrosine kinases is not secondary to Ca²⁺ mobilization and protein kinase C activation in lysophosphatidic acid-stimulated platelets.