title: Diphenylene iodonium, an inhibitor of free radical formation, inhibits platelet aggregation.
abstract: Diphenylene iodonium is an inhibitor of the enzyme NADPH-oxidase and prevents the generation of oxygen-derived free radicals in neutrophils (Cross and Jones, 1986). Here we show that diphenylene iodonium (0.25-2 microM) inhibited, according to the dose, thrombin-induced platelet-aggregation in human washed platelets and ADP-induced platelet aggregation in platelet-rich plasma. At the concentrations which inhibited platelet aggregation diphenylene iodonium did not alter platelet concentrations of cAMP or cGMP but enhanced the anti-platelet activity of iloprost, sodium nitroprusside or cultured endothelial cells. These findings highlight the importance of free radicals as platelet pro-aggregatory agents.
authors.affiliation: William Harvey Research Institute, St. Bartholomew's Medical College, London, U.K.
authors.forename: D
authors.initials: D
authors.lastname: Salvemini
authors.forename: W
authors.initials: W
authors.lastname: Radziszewski
authors.forename: V
authors.initials: V
authors.lastname: Mollace
authors.forename: A
authors.initials: A
authors.lastname: Moore
authors.forename: D
authors.initials: D
authors.lastname: Willoughby
authors.forename: J
authors.initials: J
authors.lastname: Vane
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005609:Free Radicals; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009861:Onium Compounds / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D013917:Thrombin / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; D005609:Free Radicals; D009861:Onium Compounds; D010975:Platelet Aggregation Inhibitors; C031291:diphenyliodonium; D009599:Nitroprusside; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D009247:NADH, NADPH Oxidoreductases; D013917:Thrombin; D006152:Cyclic GMP; D016285:Iloprost