Liberation of Nitric Oxide from S-Nitrosothiols

Summary

Nitric oxide (NO) has a wide variety of functions. NO generates S-nitrosothiols (RS-NO), which exhibit various activities attributable to NO. The metabolism of RS-NO, however, remains to be elucidated. RS-NO are considerably stable under physiological conditions. However, when incubated with rat liver homogenate, they rapidly disappeared from the mixture. Because such an effect was not observed with plasma, some compound(s) present in the liver might enhance the metabolism of RS-NO. Because levels of ascorbic acid and reduced glutathione (GSH) are significantly higher in cells than in plasma, effects of ascorbic acid, GSH, and other compounds were tested on the stability of RS-NO. S-Nitrosoglutathione (GS-NO) decomposed very slowly, which was accelerated by various compounds with reducing activity (ascorbic acid = cysteine > GSH). Because the cellular levels of ascorbic acid are fairly high, this compound might be an important modulator of the metabolism of RS-NO. Both NO and RS-NO reversibly inhibited the respiration of ascites tumor cells (NO > RS-NO). The inhibitory effect of RS-NO on the respiration was enhanced strongly by ascorbic acid, suggesting that ascorbic acid releases NO from RS-NO. These results suggested that ascorbic acid, cysteine, and related thiols might play important roles as modulators for RS-NO metabolism and NO action.