U-60,257 has no effect on the metabolism of arachidonic acid in nonstimulated human polymorphonuclear leukocytes.
When human polymorphonuclear leukocytes (PMNL) were incubated with exogenous 14C-arachidonic acid only traces of 5-lipoxygenase products including 5-HETE and leukotriene B4 were detected. On the other hand, considerable amounts of cyclo-oxygenase metabolites including PGE2, TXB2, HHT, PGD2, PGF2 alpha and 6-keto-PGF1 alpha as well as mono-HETE's migrating in the vicinity of 12-HETE were formed. Coincubation of PMNL with platelets did not lead to any detectable activation of the 5-lipoxygenase pathway. 10 microM U-60,257, an inhibitor of leukotriene synthesis, had no effect on the low basal 5-lipoxygenase activity nor on other lipoxygenases in either PMNL or during coincubation of PMNL with platelets. The formation of cyclo-oxygenase products was neither affected by U-60,257. It also failed to have any effect on the aggregation of PMNL induced by arachidonic acid, leukotriene B4 or platelet activating factor. The present study indicates that U-60,257, which has been reported to be a specific inhibitor of leukotriene synthesis, has no effect on the cyclo-oxygenase or on lipoxygenases other than the 5-lipoxygenase (i.e. 12- and possibly 15-) in human PMNL and obviously neither in human platelets.
D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002449:Cell Aggregation / Q000187:drug effects; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013189:SRS-A / Q000037:antagonists & inhibitors*
D001095:Arachidonic Acids; D013189:SRS-A; D016718:Arachidonic Acid; D011464:Epoprostenol; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C035296:piriprost