Effects of inhibitors of hydrogen sulphide synthesis on rat colonic motility

BACKGROUND AND PURPOSE The role of hydrogen sulphide (H2S) as a putative endogenous signalling molecule in the gastrointestinal tract has not yet been established. We investigated the effect of D, L-propargylglycine (PAG), an inhibitor of cystathionine gamma-lyase (CSE), amino-oxyacetic acid (AOAA) and hydroxylamine (HA), inhibitors of cystathionine beta-synthase (CBS) on rat colonic motility. EXPERIMENTAL APPROACH Immunohistochemistry, H2S production, microelectrode and organ bath recordings were performed on rat colonic samples without mucosa and submucosa to investigate the role of endogenous H2S in motility. KEY RESULTS CSE and CBS were immunolocalized in the colon. H2S was endogenously produced (15.6 +/- 0.7 nmol . min(-1) . g(-1) tissue) and its production was strongly inhibited by PAG (2 mM) and AOAA (2 mM). PAG (2 mM) caused smooth muscle depolarization and increased spontaneous motility. The effect was still recorded after incubation with tetrodotoxin (TTX, 1 mu M) or N-omega-nitro-Larginine (L-NNA, 1 mM). AOAA (2 mM) caused a transient (10 min) increase in motility. In contrast, HA (10 mu M) caused a 'nitric oxide-like effect', smooth muscle hyperpolarization and relaxation, which were antagonized by 1H-[ 1,2,4] oxadiazolo[ 4,3-alpha]quinoxalin-1-one (ODQ, 10 mu M). Neither spontaneous nor induced inhibitory junction potentials were modified by AOAA or PAG. CONCLUSIONS AND IMPLICATIONS We demonstrated that H2S is endogenously produced in the rat colon. PAG and AOAA effectively blocked H2S production. Our data suggest that enzymatic production of H2S regulates colonic motility and therefore H2S might be a third gaseous inhibitory signalling molecule in the gastrointestinal tract. However, possible non-specific effects of the inhibitors should be considered.