The cGMP modulator, LY83583 alters oxygen metabolites differently in cultured endothelial cells and isolated neutrophilic granulocytes.
The present study was designed to assess the effect of LY83583 on H2O2/O2- production from endothelial cells and neutrophils, as determined by chemiluminiscence generation in vitro. We found that LY83583 increased H2O2/O2-production from endothelial cells, but inhibited the H2O2/O2- production from phorbol myristate acetate-stimulated neutrophils. Furthermore, LY83583 consumed NADPH under certain conditions. Since neutrophils generate superoxide anion radicals via an NADPH-oxidase, we suggest that the reduction of chemiluminiscence, seen after addition of LY83583 to phorbol myristate acetate-stimulated neutrophils, is due to increased consumption of NADPH. In endothelial cells, NADPH is required as a co-factor in the generation of nitric oxide, which may interact with superoxide anion. A consumption in NAPDH would therefore be expected to decrease the production of nitric oxide and increase H2O2/O2-generation. The consumption of NADPH in endothelial cells could also cause reduced scavenger functions of the glutathion system, resulting in a further increase in H2O2 release.
Department of Medical Microbiology, Faculty of Health Sciences, University of Linköping, Sweden.
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Sundqvist
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Axelsson
D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008163:Luminescent Measurements; D009249:NADP / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D010084:Oxidation-Reduction; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000634:Aminoquinolines; D013189:SRS-A; D013481:Superoxides; D009249:NADP; C041715:6-anilino-5,8-quinolinedione; D006861:Hydrogen Peroxide; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate