Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract

Aims: Hydrogen sulphide (H2S) exerts several anti-inflammatory effects, accelerates the healing of experimental gastric ulcers, and can stimulate intestinal secretion. Little is known about H2S synthesis in the gastrointestinal tract. The aim of this study was to characterize H2S synthesis throughout the gastrointestinal tract.

Methods: H2S synthesis in various gastrointestinal tissues of rats and mice was determined. The effects and selectivity of inhibitors of two key enzymes for H2S synthesis, cystathionine-gamma-lyase and cystathionine-beta-synthase, were examined. Cystathionine-gamma-lyase and cystathionine-beta-synthase expression was evaluated by Western blotting and immunohistochemistry. Cystathionine-gamma-lyase and cystathionine-beta-synthase expression in biopsies of human colon was also examined.

Results: H2S synthesis was variable throughout the gastrointestinal tract in parallel with variations in cystathionine-gamma-lyase and cystathionine-beta-synthase expression. The efficacy of cystathionine-beta-synthase and cystathionine-gamma-lyase inhibitors to reduce H2S synthesis in these tissues was also variable. Cystathionine-beta-synthase is the predominant source of H2S synthesis in the colon of rodents. Cystathionine-gamma-lyase and cystathionine-beta-synthase were also expressed in healthy human colon biopsies.

Conclusions: The capacity for H2S synthesis varies throughout the rodent gastrointestinal tract, as does the distribution and contribution of the two key enzymes. Investigation of additional enzymatic sources of H2S and the development of more selective inhibitors are suggested.