Neocuproine inhibits the decomposition of endogenous S-nitrosothiol by ultraviolet irradiation in the mouse gastric fundus

Ogulener N., Ergun Y.

EUROPEAN JOURNAL OF PHARMACOLOGY, vol.485, pp.269-274, 2004 (SCI-Expanded) identifier identifier identifier


In the present study, we investigated whether copper ions are involved in the decomposition of endogenous S-nitrosothiols by ultraviolet (UV) light irradiation in the mouse gastric fundus. The effects of copper ions and chelators of copper(l) and copper(II), neocuproine and cuprozine, respectively, were studied on relaxations in response to S-nitrosoglutathione, UV irradiation, exogenous nitric oxide (NO), added as acidified NaNO2, and isoproterenol. UV irradiation of smooth muscle strips induced fast and transient relaxations which were mimicked by exogenous NO. S-Nitrosoglutathione induced concentration-dependent relaxations, which were more sustained than those elicited by UV irradiation or NO. CuCl2 did not affect relaxations elicited by UV irradiation, exogenous NO and isoproterenol but enhanced those elicited by S-nitrosoglutathione. CuSO4 but not FeSO4 Mimicked the effect Of CuCl2 on relaxations elicited by S-nitrosoglutathione. Neocuproine, the copper(I)-specific chelator, inhibited both photorelaxation and S-nitrosoglutathione-induced relaxation, and this inhibition was prevented by CuCl2. In contrast, neocuproine significantly enhanced the relaxations in response to exogenous NO, without affecting the relaxations elicited by isoproterenol. Cuprizone, a specific copper(II) chelator, did not affect relaxations in response to S-nitrosoglutathione, UV irradiation, exogenous NO and isoproterenol. These results suggest that copper(l) and not copper(II) may play a role in the NO release evoked by the light-induced decomposition of endogenous S-nitrosothiols in mouse gastric fundus. Also, results with the selective copper(l) chelator, neocuproine, confirmed our recent findings that the endogenous "store" of S-nitrosoglutathione, rather than NO, acts as an intermediate in photorelaxation of the mouse gastric fundus, and that photorelaxation may be a suitable model to elucidate the nature of endogenous S-nitrosothiols. (C) 2003 Elsevier B.V. All rights reserved.