Liberation and oxygenation of polyenoic acids in stimulated platelets.
Radiolabeled polyenoic acids were incorporated into human platelet lipids using albumin as vector. Platelets were then triggered with 0.1 or 1 U/ml thrombin, and 0.5 or 2 x 10(-6) M calcium ionophore A23187. Lipid extracts were analyzed for neutral lipids, free fatty acids, monohydroxylated acids, prostanoids and glycocerophospholipid subclasses. During platelet activation induced by thrombin or by ionophore, arachidonic and eicosapentaenoic acids were liberated from phospholipids in large amounts and were subsequently oxygenated via platelet oxygenases. Substantial amounts of lipoxygenase products and thromboxanes were produced from these acids. Liberation and oxygenation of linoleic, alpha-linolenic, and docosahexaenoic acids were much less pronounced. Polyenoic acid liberation from phospholipid subclasses also behaved quite differently. Apart from alpha-linolenic and adrenic acids, which were poorly liberated, all the others were freed from phosphatidylinositol. In addition, arachidonic, eicosapentaenoic, and 5, 8, 11-eicosatrienoic acids were liberated from phosphatidylcholine at high concentrations of agonists and partially reincorporated into phosphatidylethanolamine. Finally, linoleic acid was deacylated from phosphatidylinositol and phosphatidylserine and almost entirely reacylated into phosphatidylcholine, whereas docosahexaenoic acid was deacylated from phosphatidylcholine and phosphatidylinositol reacylated into phosphatidylethanolamine, respectively. It is concluded that these polyenoic acids, all for which modulate platelet functions, exhibit very different metabolisms. They may act via their oxygenated derivatives and/or at the membrane phospholipid level.
Hajarine
M
M
INSERM U63, Institut Pasteur, Laboratoire d'Hémobiologie Faculté Alexis Carrel, Lyon, France.
Lagarde
M
M
D001711:Biotransformation / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D002247:Carbon Isotopes; D005231:Fatty Acids, Unsaturated / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D002135:Calcium-Binding Proteins; D002247:Carbon Isotopes; D005231:Fatty Acids, Unsaturated; D010716:Phosphatidylinositols; C025673:calciphorin; D010738:Type C Phospholipases; D013917:Thrombin