Prostaglandin E and analogs of prostacyclin influencing superoxide production by the human neutrophil NADPH oxidase system.
The effects of prostaglandin (PG) E1 and I2 analogs (OP-41483 and OP-2507) on the superoxide generation of human neutrophil NADPH oxidase (EC 1.6.99.6) in both whole-cell and cell-free systems were investigated. In a whole-cell system, OP-2507 inhibited the superoxide generation by neutrophils exposed to phorbol myristate acetate concentration-dependently through its superoxide-scavenging action. The concentration of the drug required for 50% inhibition of the oxidase (IC50) was 21 microM. In a cell-free system, however, the drug in concentrations of < 100 microM did not inhibit the activation of NADPH oxidase by sodium dodecyl sulfate because of its inactivation by the detergent. Although PGE1 and OP-41483 did not inhibit the superoxide production by stimulated neutrophils in a whole-cell system, they both inhibited the activation of NADPH oxidase in a cell-free system concentration-dependently, with IC50 values of 44 and 170 microM, respectively. In addition, in the cell-free system, the Km value for NADPH of the oxidase was unchanged by PGE1. The results suggest that the PGI2 analog, OP-2507, is a possible superoxide-scavenger and that PGE1 inhibits the NADPH oxidase activation by sodium dodecyl sulfate in a cell-free system concentration-dependently.
Umeki
S
S
Department of Medicine, Toshida-kai Kumeda Hospital, Osaka, Japan.
D000527:Alprostadil / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016166:Free Radical Scavengers; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D016166:Free Radical Scavengers; D011465:Prostaglandins, Synthetic; D013481:Superoxides; C049453:OP 2507; D011464:Epoprostenol; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D000527:Alprostadil; C035847:ataprost