Decanoyl lysophosphatidic acid induces platelet aggregation through an extracellular action. Evidence against a second messenger role for lysophosphatidic acid.
Platelets rapidly convert 1,2-didecanoyl-sn-glycerol into its corresponding phosphatidic acid and lysophosphatidic acid derivatives, thereby providing a means of introducing these two compounds into platelets. 1-Decanoyl-2-lyso-3-sn-phosphatidic acid, when added directly to platelets, induced platelet aggregation and raised intracellular Ca2+ levels at concentrations of 0.3 microM upwards, but was without effect when formed intracellularly from 1,2-didecanoylglycerol at an estimated concentration of approx. 47 microM. This indicates that the site of platelet activation by lysophosphatidic acid is extracellular. A concentration of thrombin (0.2 unit/ml), which produced maximal platelet aggregation, caused an estimated intracellular formation of 20 microM-lysophosphatidic acid in the presence of 2 mM-Ca2+; however, there was no detectable release of lysophosphatidic acid into the bathing medium. Lysophosphatidic acid, therefore, may not be an intracellular second messenger involved in platelet aggregation by thrombin.
D000634:Aminoquinolines / Q000378:metabolism; D002855:Chromatography, Thin Layer; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D008246:Lysophospholipids; D010712:Phosphatidic Acids / Q000097:blood* / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology
D000634:Aminoquinolines; D007295:Inositol Phosphates; D008246:Lysophospholipids; D010712:Phosphatidic Acids; C047605:1-decanoyl-2-lyso-3-phosphatidic acid; D013917:Thrombin; C035739:Quin2; D007213:Indomethacin