Time-dependent inhibition of the cyclooxygenase pathway by 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid.
We examined effects of small dose (1 microM or less) of exogenous 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) on the formation of cyclooxygenase products from exogenous arachidonic acid (AA) in washed human platelets. With a simultaneous addition of AA, 12-HPETE did not affect the formation of thromboxane (TX)B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT). However, by being preincubated with platelets before an addition of AA, 0.1 microM or greater of 12-HPETE inhibited the formation of TXB2 and HHT dose-dependently. In addition, the inhibitory effect of 12-HPETE increased as the preincubation time was prolonged. These results suggest that 12-HPETE is a strong inhibitor for the cyclooxygenase pathway.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D015289:Leukotrienes; D013929:Thromboxane B2 / Q000096:biosynthesis; D013997:Time Factors
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D016718:Arachidonic Acid; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C021201:12-HPETE