title: Hydrogen sulfide-mediated regulation of contractility in the mouse ileum with electrical stimulation: roles of L-cysteine, cystathionine β-synthase, and K+ channels.
abstract: Hydrogen sulfide (H2S) is considered to be a signaling molecule. The precise mechanisms underlying H2S-related events, including the producing enzymes and target molecules in gastrointestinal tissues, have not been elucidated in detail. We herein examined the involvement of H2S in contractions induced by repeated electrical stimulations (ES). ES-induced contractions were neurotoxin-sensitive and increased by aminooxyacetic acid, an inhibitor of cystathionine β-synthase (CBS) and cystathionine γ-lyase, but not by D,L-propargylglycine, a selective inhibitor of cystathionine γ-lyase, in an ES trial-dependent manner. ES-induced contractions were markedly decreased in the presence of L-cysteine. This response was inhibited by aminooxyacetic acid and an antioxidant, and accelerated by L-methionine, an activator of CBS. The existence of CBS was confirmed. NaHS transiently inhibited ES- and acetylcholine-induced contractions, and sustainably decreased basal tone for at least 20 min after its addition. The treatment with glibenclamide, an ATP-sensitive K+ channel blocker, reduced both the L-cysteine response and NaHS-induced inhibition of contractions. The NaHS-induced decrease in basal tone was inhibited by apamin, a small conductance Ca2+-activated K+ channel blocker. These results suggest that H2S may be endogenously produced via CBS in ES-activated enteric neurons, and regulates contractility via multiple K+ channels in the ileum.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamane
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kanno
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Fujino
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan. Electronic address: murayama-toshi@faculty.chiba-u.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Murayama
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D003545:Cysteine / Q000502:physiology*; D004558:Electric Stimulation; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007082:Ileum / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000494:pharmacology; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000625:Aminooxyacetic Acid; D001030:Apamin; D008715:Methionine; D003541:Cystathionine beta-Synthase; D003545:Cysteine; D000109:Acetylcholine; D006862:Hydrogen Sulfide
keywords: Contractility; Hydrogen sulfide; K(ATP) channels; Mouse ileum; SK(Ca) channels; l-Cysteine