Role of Hydrogen Sulfide as a Gasotransmitter in Modulating Contractile Activity of Circular Muscle of Rat Jejunum

Aim Our aim was to determine mechanisms of action of the gasotransmitter hydrogen sulfide (H2S) on contractile activity in circular muscle of rat jejunum. Methods Jejunal circular muscle strips were prepared to measure isometric contractions. Effects of sodium hydrosulfide (NaHS), a H2S donor, were evaluated on spontaneous contractile activity and after pre-contraction with bethanechol. L-Cysteine was evaluated as an endogenous H2S donor. We evaluated extrinsic nerves, enteric nervous system, visceral afferent nerves, nitric oxide, K-ATP(+) and K-Ca(+) channels, and myosin light chain phosphatase on action of H2S using non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, L-N-G-nitro arginine (L-NNA), glibenclamide, apamin, and calyculin A, respectively, and electrical field stimulation (EFS). Results NaHS dose-dependently and reversibly inhibited spontaneous and bethanechol-stimulated contractile activity (p<0.05). L-Cysteine had a dose-dependent inhibitory effect. Non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, L-NNA, or apamin had no effect on contractile inhibition by NaHS; in contrast, low-dose glibenclamide and calyculin A prevented NaHS-induced inhibition. We could not demonstrate H2S release by EFS. Conclusions H2S inhibits contractile activity of jejunal circular muscle dose-dependently, in part by K-ATP(+) channels and via myosin light chain phosphatase, but not via pathways mediated by the extrinsic or enteric nervous system, visceral afferent nerves, nitric oxide, or K-Ca(+) channels.