The hypothesis of the main role of H2S in coupled sulphide-nitroso signalling pathway.

As a part of the nitroso signalling pathway, nitroso-compounds serve as stores and carriers of NO; as part of the sulphide signalling pathway, bound sulfane-sulphur compounds serve as stores and carriers of H2S. Here we hypothesise a coupled sulphide-nitroso signalling pathway, in which H2S plays a main role. H2S releases NO from the endogenous S-nitroso-compounds nitroso-cysteine, nitroso-acetylcysteine and nitroso-albumin. Relaxation of noradrenaline-precontracted aortic rings by H2S is also enhanced in the presence of nitroso-albumin, which may implicate the involvement of the nitroso signalling pathway. Pretreatment of albumin, cysteine, N-acetylcysteine and lipids with H2S results in binding of sulphur to these compounds creating thus new-modified sulphur compounds that release NO from nitroso-compounds directly and/or through released H2S, which suggests sulphide-nitroso signalling pathway participation. This hypothesis is supported by the observation that the pretreatment of noradrenaline-precontracted aortic rings with H2S significantly enhanced relaxation induced by nitroso-glutathione in the absence of H2S. We assume that the NO release from nitroso-compounds directly by H2S or indirectly by the H2S-induced sulphur-bound compounds represents coupled sulphide-nitroso signalling, which may explain some of the numerous biological effects of H2S that are shared with NO.