title: Effects of inhibitors of hydrogen sulphide synthesis on rat colonic motility.
abstract: OBJECTIVE
  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 γ-lyase (CSE), amino-oxyacetic acid (AOAA) and hydroxylamine (HA), inhibitors of cystathionine β-synthase (CBS) on rat colonic motility.
  
  
  METHODS
  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.
  
  
  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 µM) or N(ω) -nitro-L-arginine (L-NNA, 1 mM). AOAA (2 mM) caused a transient (10 min) increase in motility. In contrast, HA (10 µM) caused a 'nitric oxide-like effect', smooth muscle hyperpolarization and relaxation, which were antagonized by 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, 10 µM). Neither spontaneous nor induced inhibitory junction potentials were modified by AOAA or PAG.
  
  
  CONCLUSIONS
  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 ight be a third gaseous inhibitory signalling molecule in the gastrointestinal tract. However, possible non-specific effects of the inhibitors should be considered.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Gil
authors.forename: D
authors.initials: D
authors.lastname: Gallego
authors.forename: M
authors.initials: M
authors.lastname: Jiménez
mesh_terms: D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019811:Hydroxylamine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: C112418:32-ascomycinyloxyacetic acid; D000480:Alkynes; D004791:Enzyme Inhibitors; D019811:Hydroxylamine; D009569:Nitric Oxide; D013779:Tetrodotoxin; C009055:propargylglycine; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D003545:Cysteine; D005998:Glycine; D016559:Tacrolimus; D006862:Hydrogen Sulfide