S-nitrosothiols and the bioregulatory actions of nitrogen oxides through reactions with thiol groups

The reactivity of selected RS-NOs has led to the misconception that these compounds are uniformly unstable under physiological conditions. Moreover, current evidence supports the notion that biological responses elicited by RS-NOs may result from either liberation of nitric oxide or from NO group transfer chemistry involving either NO+ or NO-. Some evidence suggests that such reactions may be enzymatically controlled. The data supporting the potential biological relevance of RS-NOs include: (1) evidence that these compounds form under physiological conditions; (2) their identification in insects, lower mammals, and several human biological systems; and (3) findings that RS-NOs possess a wide range of biological activities, including antimicrobial effects, vasodilation, platelet inhibition, bronchodilation and inhibition of intestinal motility, while being relatively resistant to reactions with O2 and O2- associated with NO. toxicity. It is further noteworthy that biological activity of RS-NO is often not related to the propensity to liberate NO., and these adducts are generally more potent and selective in their action than NO. itself (Stamler et al. 1989; Cooke et al. 1990; Rockett et al. 1991; Jansen et al. 1991; Lipton et al. 1993). The data presented here support the idea that RS-NO may be involved in stabilizing nitric oxide-like bioactivity, in transporting and targeting the NO group to specific (thioregulatory) effector sites, in mitigating the cytotoxic effects of nitric oxide that result from reaction with oxygen species, and may serve to regulate protein function in a posttranslational modification akin, perhaps, to phosphorylation. The recently demonstrated NO group transfer reactions to plasma membrane proteins containing reactive sulfhydryls (Lipton et al. 1993; Stamler 1994) also raises the possibility of signal transduction initiated through more traditional "agonist-receptor" mediated pathways.