Conversion of arachidonic acid to two novel products by a cytochrome P450-dependent mixed-function oxidase in polymorphonuclear leukocytes.
Canine polymorphonuclear leukocytes metabolize [14C] arachidonic acid into 2 unidentified products, separated by thin-layer chromatography and high performance liquid chromatography, and called peak 1 and peak 2. The formation of peak 1 is maximal at 5 minutes and then declines, while the synthesis of peak 2 increases throughout the 30 minute incubation period. The formation of peak 1 and, to a lesser extent, peak 2, was enhanced after dual inhibition of lipoxygenase and cyclo-oxygenase enzymes with BW755C (94 microns) or nafazatrom (37 microns), or after incubation in a calcium-free buffer. In contrast, the formation of these products was inhibited by SKF-525A (50 microns), suggesting a cytochrome P450-dependent mechanism. The presence of cytochrome P450 in neutrophil microsomes was confirmed by measuring aryl hydrocarbon hydroxylase activity and cytochrome P450 content.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D016861:Cyclooxygenase Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000097:blood*; D004285:Dogs; D016859:Lipoxygenase Inhibitors; D006899:Mixed Function Oxygenases / Q000097:blood*; D009504:Neutrophils / Q000201:enzymology*
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases