In vitro incorporation and metabolism of some icosaenoic acids in platelets. Effect on arachidonic acid oxygenation.
Three icosaenoic acids (20:3(n-6), 20:5(n-3) and 20:3(n-9)) which may arise in platelet phospholipids under certain dietary conditions and which may affect platelet functions have been taken up by human platelets. Each acid was pre-coated onto delipidated albumin and then incubated with platelets isolated from their plasma. The distribution study of each acid in cellular lipids revealed that around 80% of the acid taken up was located in phospholipids, of which the bulk was in phosphatidylcholine. The percentage incorporation of each acid into the different glycerophospholipids was similar to their endogenous percentage profiles, therefore simulating the in vivo situation. The icosaenoic acids then incorporated were liberated from phospholipids when platelets were incubated with thrombin or calcium ionophore A23187 and subsequently oxygenated through the cyclooxygenase and/or lipoxygenase pathway. Whereas 20:3(n-6) was readily converted into cyclooxygenase products, 20:5(n-3) was more specifically converted into lipoxygenase products, and this latter conversion was comparable to that of 20:3(n-9) which is not a prostanoid precursor. Finally, only 20:3(n-6)- or 20:5(n-3)-rich platelets exhibited a reduced availability of endogenous arachidonic acid from phospholipids when induced by thrombin. It is concluded that inhibitory polyunsaturated fatty acids (20:3(n-6) and 20:5(n-3)) could act both by reducing prostaglandin H2/thromboxane A2 production from endogenous arachidonic acid and in generating platelet inhibitory substances (cyclooxygenase and/or lipoxygenase products of 20:3(n-6) and 20:5(n-3)). On the other hand, 20:3(n-9), a fatty acid which potentiates platelet aggregation through its lipoxygenase end product, could produce sufficient amounts of this compound to enhance the aggregation when platelets are triggered with inducers of phospholipase activity such as thrombin or calcium ionophore.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D004537:Eicosanoic Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008563:Membrane Lipids / Q000378:metabolism; D010084:Oxidation-Reduction; D010712:Phosphatidic Acids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D010712:Phosphatidic Acids; D010743:Phospholipids; D016718:Arachidonic Acid; D000001:Calcimycin; D013917:Thrombin