Hydrogen Sulfide Modulates Contractile Function in Rat Jejunum

BackgroundEffects of hydrogen sulfide (H2S), a third gasotransmitter of the gut, are not well understood. The aim of this study was to determine effects/mechanisms of H2S action on contractile function in rat jejunal muscle.MethodsTransmural strips of longitudinal muscle were evaluated. Response to sodium hydrosulfide (NaHS, H2S donor; 10−5–10−3M) was studied on spontaneous contractile activity and after precontraction (bethanechol, 3 × 10−6M). Atropine, propranolol, phentolamine, tetrodotoxin, capsaicin, L-NG-nitro arginine (L-NNA), and glibenclamide were used to determine mechanisms. L-cysteine (10−4–10−2M; substrate for H2S production) and aminooxyacetic acid and DL-propargylglycine (inhibitors of enzymes generating H2S endogenously) were used to study endogenous production. Aminooxyacetic acid, DL-propargylglycine, L-NNA, and vasoactive intestinal polypeptide (VIP) antagonist [D-p-Cl-Phe6,Leu17]-VIP were used to study H2S release during electrical field stimulation (EFS) and interaction with VIP and nitric oxide. Immunohistofluorescence of jejunal whole mounts was performed for endogenous H2S-producing enzymes.ResultsCystathionine-β-synthase and cystathionine-γ-lyase were expressed only in myenteric plexus. NaHS suppressed spontaneous and stimulated contractile activity (P < 0.01). Glibenclamide prevented some suppression by NaHS (P = 0.01) of stimulated contractile activity but did not prevent suppression of spontaneous contractile activity. Other drugs had no effect on spontaneous contractile activity but increased inhibitory effects of NaHS on spontaneous and stimulated contractile activity (P < 0.05). L-cysteine had no effects on contractile activity. Inhibitors altered basal and stimulated activity suggesting endogenous release of H2S.ConclusionsH2S presumably suppresses contractile activity in jejunum by direct effects on smooth muscle. Mechanism(s) of inhibition remains unclear, because blocking known neurotransmitters enhanced H2S-induced suppression, while blocking adenosine triphosphate (ATP)-sensitive K+-channels did not block H2S-induced inhibition.