The adrenochrome pathway. A potential catabolic route for adrenaline metabolism in inflammatory disease.
Polymorphonuclear leukocytes activated by latex (polystyrene) beads or the chemotactic peptide N-formyl Met Leu Phe stimulated the oxidation of adrenaline (0.3 microM-10 mM) to adrenochrome, detected spectrophotometrically at 480 nm or by a high-performance liquid chromatographic (HPLC) method. This oxidation was detectable within 5 min and continued for at least 4 hr. Over the concentration range 0.3-10 microM, more than 80% of the adrenaline oxidation occurred via the adrenochrome pathway rather than the amine oxidase-catechol methyltransferase pathway. Medium isolated after stimulation of the polymorphonuclear leukocytes retained the ability to oxidize adrenaline to adrenochrome. Serum from patients after myocardial infarction induced more oxidation of adrenaline to adrenochrome than control serum. Superoxide dismutase, catalase, and azide inhibited by 70-95% the oxidation of adrenaline to adrenochrome, either by cells or medium. Commercially available adrenochrome was biologically active, but some of the actions were due to contaminants of the preparation. HPLC of an extract of synovial fluid from a patient with rheumatoid arthritis, a fluid that contains polymorphonuclear leukocytes, showed a peak identical to that of the adrenochrome standard. The results provide a cellular mechanism for adrenochrome formation and preliminary evidence that adrenochrome can be produced in inflammatory conditions in which polymorphonuclear leukocyte infiltration occurs.
D000323:Adrenochrome / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D001386:Azides / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004837:Epinephrine / Q000378:metabolism*; D005110:Extracellular Space / Q000201:enzymology; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D009203:Myocardial Infarction / Q000201:enzymology*; D009504:Neutrophils / Q000201:enzymology; D010084:Oxidation-Reduction / Q000187:drug effects; D010544:Peroxidases / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D013053:Spectrophotometry; D013482:Superoxide Dismutase / Q000494:pharmacology; D013582:Synovial Fluid / Q000201:enzymology
D001386:Azides; D000323:Adrenochrome; D010544:Peroxidases; D002374:Catalase; D013482:Superoxide Dismutase; D006596:Hexosaminidases; D004837:Epinephrine