Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract☆

Abstract 

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-γ-lyase and cystathionine-β-synthase, were examined. Cystathionine-γ-lyase and cystathionine-β-synthase expression was evaluated by Western blotting and immunohistochemistry. Cystathionine-γ-lyase and cystathionine-β-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-γ-lyase and cystathionine-β-synthase expression. The efficacy of cystathionine-β-synthase and cystathionine-γ-lyase inhibitors to reduce H₂S synthesis in these tissues was also variable. Cystathionine-β-synthase is the predominant source of H₂S synthesis in the colon of rodents. Cystathionine-γ-lyase and cystathionine-β-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.

Keywords: Cystathionine-γ-lyase, Cystathionine-β-synthase, Gastrointestinal, Hydrogen sulphide, Inflammation, Propargylglycine, Ulcer