title: Nitric oxide production from macrophages is regulated by arachidonic acid metabolites.
abstract: In activated macrophages the inducible form of the enzyme nitric oxide (NO) synthase generates high amounts of the toxic mediator NO. After 20 h of treatment with LPS rat peritoneal macrophages release 12-16 nmol NO2-/10(5) cells which is detectable in the culture supernatant by the Griess reaction as a measure of NO formation. The addition of aminoguanidine (1 mM), a preferential inhibitor of the inducible NO-synthase, completely abolished NO2-accumulation. Incubation with indomethacin or acetyl-salicylic acid, preferential inhibitors of the cyclooxygenase pathway of the arachidonic acid metabolism, did not influence NO2- levels. Nordihydro-guaiaretic acid (50 microM), a preferential inhibitor of the lipoxygenase pathway, caused strong reduction of NO2- accumulation to 1.9 +/- 0.3 nmol/200 microliter. Simultaneous inhibition of cyclo- and lipoxygenase by BW755c resulted in an intermediate effect (7.3 +/- 1.1 nmol/200 microliter NO2-). These results show that the induction of NO production in activated macrophages is regulated by products of the lipoxygenase-pathway of the arachidonic acid metabolism.
authors.affiliation: Diabetes Research Institute, University of Düsseldorf, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Imai
authors.forename: H
authors.initials: H
authors.lastname: Kolb
authors.forename: V
authors.initials: V
authors.lastname: Burkart
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000378:metabolism*; D009637:Masoprocol / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016861:Cyclooxygenase Inhibitors; D009573:Nitrites; D016718:Arachidonic Acid; D009569:Nitric Oxide; D009637:Masoprocol; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases