ACTIVATION OF HUMAN PLATELETS BY LYSOPHOSPHATIDIC ACID

The biochemical mechanisms of platelet activation by lysophosphatidic acid were investigated. Lysophosphatidic acid interacts with a membran e receptor coupled to the inhibitory GTP-binding protein Gi and produc es a rapid decrease of the intracellular concentration of cAMP. Aggreg ation 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 lysophosp hatidic acid in the absence of extracellular CaCl2 does not involve ph ospholipase C activation, as evaluated by measuring mobilization of Ca 2+ from internal stores and pleckstrin phosphorylation, but causes the rapid tyrosine phosphorylation of several intracellular proteins. Our results indicate that activation of intracellular indicate that activ ation of intracellular tyrosine kinases is not secondary to Ca2+ mobil ization and protein kinase C activation in lysophosphatidic acid-stimu lated platelets.