Potential role of the gaseous mediator hydrogen sulphide (H2S) in inhibition of human colonic contractility

BackgroundHydrogen 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.MethodsHuman 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.ResultsCombination of PAG and AOAA depolarized the smooth muscle (5-6 mV, n = 4) and elicited a transient increase in tone (260.5 ± 92.8 mg, n = 12). No effect was observed on neural mediated inhibitory junction potential or relaxation. In the presence of tetrodotoxin 1 μM, NaHS concentration-dependently inhibited spontaneous contractions (EC50 = 329.2 μM, n = 18). This effect was partially reduced by the guanylyl cyclase inhibitor ODQ 10 μM (EC50 = 2.6 μM, n = 12) and by l-NNA 1 mM (EC50 = 1.4 mM, n = 8). NaHS reversibly blocked neural mediated cholinergic (EC50 = 2 mM) and tachykinergic (EC50 = 5.7 mM) contractions. NaHS concentration-dependently reduced the increase in spontaneous mechanical activity (AUC) induced by carbachol (EC50 = 1.9 mM) and NKA (EC50 = 1.7 mM AUC).ConclusionsH2S 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.