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 (H ₂S) 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 H ₂S donor, were evaluated on spontaneous contractile activity and after pre-contraction with bethanechol. l-Cysteine was evaluated as an endogenous H ₂S 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 H ₂S 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 H ₂S release by EFS. Conclusions: H ₂S 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.