Differential effects of anti-inflammatory drugs on lipoxygenase and cyclo-oxygenase activities of neutrophils from a reverse passive Arthus reaction.
Rat neutrophils isolated from four-hour reverse passive Arthus reaction pleural exudates actively metabolize arachidonic acid. Production of 11-hydroxy- and 15-hydroxy-icosatetraenoic acid and 12-hydroxy-heptadecatrienoic acid is inhibited by indomethacin, benoxaprofen, BW 755C, piroxicam, ibuprofen, timegadine, and naproxen, suggesting that production of these arachidonic acid metabolites occurs at similar enzymic active sites. In addition, in the presence of the calcium inophore A23187 or the non-ionic detergent, BRIJ 56, rat neutrophils also produce the lipoxygenase products 5-hydroxy-icosatetraenoic acid and leukotriene B. The production of these metabolites is calcium dependent. Moreover, the calcium ionophore A23187 and BRIJ 56 synergistically act to augment the metabolism of exogenously added arachidonic acid via lipoxygenase. The formation of these metabolites is inhibited by BW 755C, benoxaprofen and timegadine but not by other non-steroidal anti-inflammatory drugs tested. In fact, at doses which inhibit cyclo-oxygenase activity, indomethacin, naproxen, and ibuprofen stimulate arachidonic acid metabolism via lipoxygenase.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D001183:Arthus Reaction / Q000201:enzymology*; D016861:Cyclooxygenase Inhibitors; D004789:Enzyme Activation / Q000187:drug effects; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D008297:Male; D009504:Neutrophils / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases