We hypothesized that tobacco smoke influenced smooth muscle relaxation by decreasing H2S levels and this effect could also influence expression of cystathionine γ-lyase (CSE) and sulfonylurea receptor-2 (SUR-2).
In colonic smooth muscle from rabbit, mouse, and human, l-cysteine, substrate of cystathionine-γ-lyase (CSE), or NaHS, an H<sub>2</sub>S donor, inhibited phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels, IP<sub>3</sub> receptor phosphorylation at Ser<sup>1756</sup> (measured as a proxy for PKG activation), and muscle relaxation in response to NO donor <i>S-</i>nitrosoglutathione (GSNO), suggesting augmentation of cGMP/PKG pathway by H<sub>2</sub>S.