The cGMP Modulator, LY83583 Alters Oxygen Metabolites Differently in Cultured Endothelial Cells and Isolated Neutrophilic Granulocytes (original) (raw)

1993, Pharmacology & Toxicology

The present study was designed to assess the effect of LY83583 on H,OZ/O,-production from endothelial cells and neturophils, as determined by chemiluminiscence generation in vitro. We found that LY83583 increased H,02/0,production from endothelial cells, but inhibited the H20,/0,-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 H,O,/ 0,-generation. The consumption of NADPH in endothelial cells could also cause reduced scavenger functions of the glutathion system, resulting in a further increase in H,02 release.