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 EC 50 of 0.2 μM and a maximal effect at 1 μM. Quinacrine did not modify the dependence of NO release on extracellular l -arginine. Acceleration or deceleration of O 2 − 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 O 2 − produced by xanthine oxidation. In the presence of quinacrine, agonist-induced NO release became Mg 2+ -independent and could not be attributed to an inhibition of phospholipase A 2 activity. Quinacrine made NO release insensitive to Cu 2+ chelation. The present study demonstrates that acute treatment by low quinacrine concentrations increases endothelial NO release, possibly through an inhibition of O 2 − production.