Arachidonate 5-lipoxygenase and its new inhibitors.
The 5-lipoxygenases of guinea pig peritoneal polymorphonuclear leukocytes and of rat basophilic leukemia cells have been solubilized, purified partially by affinity chromatography, and shown to convert arachidonic acid principally to 5-hydroperoxy-6,8,11,14- eicosatetraenoic acid. The activity of both 5-lipoxygenases is calcium dependent and enhanced by adenosine triphosphate and other nucleotides in the presence of calcium ion. Both 5-lipoxygenase activity and leukotriene generation by sensitized guinea pig lung tissue challenged with antigen were suppressed substantially by specific benzoquinone and flavonoid inhibitors. The in vivo significance of the findings will be explored with potent and selective lipoxygenase inhibitors, which are delineated in the 5-lipoxygenase model systems.
D000818:Animals; D001091:Arachidonate Lipoxygenases; D001491:Basophils / Q000201:enzymology; D016227:Benzoquinones; D002460:Cell Line; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D006168:Guinea Pigs; D007700:Kinetics; D007942:Leukemia, Experimental / Q000201:enzymology*; D008084:Lipoxygenase / Q000302:isolation & purification; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000201:enzymology; D009119:Muscle Contraction / Q000187:drug effects; D009504:Neutrophils / Q000201:enzymology*; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D013189:SRS-A / Q000494:pharmacology
D016227:Benzoquinones; D047309:Flavones; D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; D011809:Quinones; D013189:SRS-A; C039824:cirsiliol; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase