title: Potential role of the gaseous mediator hydrogen sulphide (H2S) in inhibition of human colonic contractility.
abstract: BACKGROUND
  Hydrogen sulphide (H2S) is an endogenous signalling molecule that might play a physiologically relevant role in gastrointestinal motility. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are two enzymes responsible for H2S production. d,l-Propargylglycine (PAG) is a CSE inhibitor whereas both aminooxyacetic acid (AOAA) and hydroxylamine (HA) are CBS inhibitors. The characterization of H2S responses and its mechanism of action are crucial to define H2S function.
  
  
  METHODS
  Human colonic strips were used to investigate the role of H2S on contractility (muscle bath) and smooth muscle electrophysiology (microelectrodes). NaHS was used as a H2S donor.
  
  
  RESULTS
  Combination of PAG and AOAA depolarized the smooth muscle (5-6mV, n=4) and elicited a transient increase in tone (260.5±92.8mg, n=12). No effect was observed on neural mediated inhibitory junction potential or relaxation. In the presence of tetrodotoxin 1μM, NaHS concentration-dependently inhibited spontaneous contractions (EC50=329.2μM, n=18). This effect was partially reduced by the guanylyl cyclase inhibitor ODQ 10μM (EC50=2.6μM, n=12) and by l-NNA 1mM (EC50=1.4mM, n=8). NaHS reversibly blocked neural mediated cholinergic (EC50=2mM) and tachykinergic (EC50=5.7mM) contractions. NaHS concentration-dependently reduced the increase in spontaneous mechanical activity (AUC) induced by carbachol (EC50=1.9mM) and NKA (EC50=1.7mM AUC).
  
  
  CONCLUSIONS
  H2S might be an endogenous gasomediator regulating human colonic contractility. Its inhibitory effect is observed at high concentrations and could be mediated by a direct effect on smooth muscle with a possible synergistic effect with NO, as well as by an interaction with the cholinergic and tachykinergic neural mediated pathways.
authors: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: M
authors: M
authors: Martinez-Cutillas
authors: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: V
authors: V
authors: Gil
authors: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: N
authors: N
authors: Mañé
authors: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain; Fundació de Gastroenterologia Dr Vilardell and Department of Surgery, Hospital de Mataró, Mataró, Barcelona, Spain.
authors: P
authors: P
authors: Clavé
authors: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain.
authors: D
authors: D
authors: Gallego
authors: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain.
authors: M T
authors: MT
authors: Martin
authors: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain. Electronic address: marcel.jimenez@uab.es.
authors: M
authors: M
authors: Jimenez
mesh_terms: D000480:Alkynes / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors; D004558:Electric Stimulation; D064426:Gasotransmitters / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D019811:Hydroxylamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D064426:Gasotransmitters; D013440:Sulfides; D000625:Aminooxyacetic Acid; D019811:Hydroxylamine; C009055:propargylglycine; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D005998:Glycine; D006862:Hydrogen Sulfide
keywords: Contractility; Human colonic smooth muscle; Hydrogen sulphide (H(2)S); Inhibitory junction potential