LYSOPHOSPHATIDIC ACIDS - INFLUENCE ON PLATELET-AGGREGATION AND INTRACELLULAR CALCIUM FLUX

Abstract

Decanoyl-, palmitoyl- and oleoyl-lysophosphatidic acid (LPA) were studied for their effects on platelet aggregation and intracellular Ca flux. Palmitoyl-LPA and oleoyl-LPA both caused a concentration-dependent aggregation of human blood platelets at concentrations of 12-300 .mu.M. Aggregation by ADP was enhanced at slightly lower concentrations. First-wave aggregation induced by the LPA was not blocked by aspirin, indomethacin or heparin, suggesting similarities to ADP aggregation. In washed platelets with a high Ca concentration, no serotonin secretion was seen, even though full aggregation occurred, suggesting that aggregation was not due to released ADP. This concept was supported by studies of platelets deficient in the storage pool of ADP and serotonin, which had a normal 1st wave aggregation response to palmitoyl-LPA. Aggregation induced by palmitoyl-LPA was inhibited by prostaglandin E1 (PGE1), theophylline and EDTA, though in the presence of EDTA shape change occurred. Aggregation stimulated by palmitoyl-LPA or oleoyl-LPA was characterized by changes in the shape of the platelets with development of pseudopods and centralization of granules closely surrounded by contractile microfilaments and supporting microtubules. The addition of palmitoyl-LPA and oleoyl-LPA, but not decanoyl-LPA, caused the release of Ca from a platelet membrane fraction that contains elements of the intracellular Ca storage system and actively concentrates this cation in the presence of ATP and Mg. Apparently LPA cause aggregation by stimulating the release of Ca intracellularly.