Occurrence of the 15-hydroxy derivative of dihomogammalinolenic acid in human platelets and its biological effect.
Various polyunsaturated fatty acids are oxygenated by platelet lipoxygenase at the n - 9 position. The present paper reports that platelets may also oxygenate dihomogammalinolenic acid (20:3(n - 6)) at the n - 6 position, leading to the formation of substantial amounts of 15-OH-8,11,13-20:3 characterized by its ultraviolet spectrum, HPLC and GC-MS analysis. Its formation was inhibited by aspirin and eicosatetraynoic acid, but not by heneicosatetraynoic acid, a specific inhibitor of platelet lipoxygenase. The time-course of its synthesis was very close to that of 12-OH-8,10-17:2 (HHD), the non-cyclic cyclooxygenase side-product, but different from that of 12-OH-8,10,14-20:3, the platelet lipoxygenase end-product of 20:3 (n - 6). Overall, these results indicate that 15-OH-20:3 could be a cyclooxygenase metabolite generated in an aborted process. Like other monohydroxy derivatives of polyenoic fatty acids, 15-OH-20:3 was able to modulate thromboxane-induced platelet aggregation. The derivative exhibited a biphasic effect on the aggregation. It potentiated at concentrations below 2.10(-7) M and inhibited at higher doses. It is concluded that the potentiating activity might explain at least part of the transient enhancement of the platelet activation observed in adding exogenous 20:3(n - 6).
Guichardant
M
M
Institut Pasteur, INSERM U63, Lyon, France.
Naltachayan-Durbin
S
S
Lagarde
M
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000097:blood*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D004357:Drug Synergism; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D007975:Leukotriene B4; D008042:Linolenic Acids / Q000097:blood* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic
D005231:Fatty Acids, Unsaturated; D008042:Linolenic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; C035510:15-hydroxy-8,11,13-eicosatrienoic acid; D007975:Leukotriene B4; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015126:8,11,14-Eicosatrienoic Acid; D001241:Aspirin