title: Quinacrine increases endothelial nitric oxide release: role of superoxide anion.
abstract: The effect of acute quinacrine treatment on agonist-induced nitric oxide (NO) release was investigated in cultured human endothelial cells using electrochemical monitoring of the in situ NO concentration. Quinacrine dose-dependently increased NO release with an apparent EC50 of 0.2 microM and a maximal effect at 1 microM. Quinacrine did not modify the dependence of NO release on extracellular L-arginine. Acceleration or deceleration of O2- dismutation, which altered NO release in control cells, did not modify it in quinacrine-treated cells. Quinacrine did not modify NO amperometric signal or reaction with O2- produced by xanthine oxidation. In the presence of quinacrine, agonist-induced NO release became Mg2+ -independent and could not be attributed to an inhibition of phospholipase A2 activity. Quinacrine made NO release insensitive to Cu2+ chelation. The present study demonstrates that acute treatment by low quinacrine concentrations increases endothelial NO release, possibly through an inhibition of O2- production.
authors.affiliation: Pharmacologie, CNRS UMR 8604, Université René Descartes, Faculté de Médecine Necker, 156, rue de Vaugirard, 75015, Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: David-Dufilho
authors.forename: Annie
authors.initials: A
authors.lastname: Brunet
authors.forename: Christelle
authors.initials: C
authors.lastname: Privat
authors.forename: Marie Aude
authors.initials: MA
authors.lastname: Devynck
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D011796:Quinacrine / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D019820:Xanthine / Q000378:metabolism
chemical_list: D013481:Superoxides; D019820:Xanthine; D009569:Nitric Oxide; D013917:Thrombin; D011796:Quinacrine