Pharmacologic modulation by prostaglandin E1 of superoxide anion production by human polymorphonuclear leukocytes.
Inhibition by prostaglandin E1 (PGE1) of superoxide anion (O2-.) production by isolated intact human neutrophils (PMNs) was investigated utilizing initial-velocity enzyme kinetics. Lag time, linearity, rate, and extent of reaction were simultaneously examined. Dose-response data indicate progressive PGE1-induced suppression of O2-. synthesis by activated PMNs with a Ki value of 0.50 and 0.98 mumol/L for initial velocity and extent of reaction, respectively. There were no significant dose-related trends for either lag time or linearity for reactions with PGE1 concentrations less than 10(-6) mol/L; however, at concentrations of 10(-8) mol/L and greater, the length of reaction was progressively shortened. PGE1 inhibition of PMN-induced O2-. production does not involve PMN activation/desensitization since PGE1 itself cannot stimulate O2-. generation. Moreover, PGE1 does not function as a free-radical scavenger. These data indicate the clinical feasibility of utilizing PGE1 to titrate PMN-induced synthesis of active oxygen metabolites, in order to attenuate PMN-associated host autoinjury.
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology*; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000097:blood*
D005609:Free Radicals; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme; D000527:Alprostadil