title: L-Cysteine/D,L-homocysteine-regulated ileum motility via system L and B°(,+) transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments.
abstract: Previous studies including ours demonstrated that L-cysteine treatments decreased motility in gastrointestinal tissues including the ileum via hydrogen sulfide (H2S), which is formed from sulfur-containing amino acids such as L-cysteine and L-homocysteine. However, the amino acid transport systems involved in L-cysteine/L-homocysteine-induced responses have not yet been elucidated in detail; therefore, we investigated these systems pharmacologically by measuring electrical stimulation (ES)-induced contractions with amino acids in mouse ileum preparations. The treatments with L-cysteine and D,L-homocysteine inhibited ES-induced contractions in ileum preparations from fasted mice, and these responses were decreased by the treatment with 2-aminobicyclo[2.2.1]heptane-2-carboxylate (BCH), an inhibitor of systems L and B°(,+). The results obtained using ileum preparations and a model cell line (PC12 cells) with various amino acids and BCH showed that not only L-cysteine, but also aminooxyacetic acid and D,L-propargylglycine, which act as H2S synthesis inhibitors, appeared to be taken up by these preparations/cells in L and B°(,+) system-dependent manners. The L-cysteine and D,L-homocysteine responses were delayed and abolished, respectively, in ileum preparations from fed mice. Our results suggested that the regulation of ileum motility by L-cysteine and D,L-homocysteine was dependent on BCH-sensitive systems, and varied depending on feeding in mice. Therefore, the effects of aminooxyacetic acid and D,L-propargylglycine on transport systems need to be considered in pharmacological analyses.
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: Ryouya
authors.initials: R
authors.lastname: Nomura
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: Madoka
authors.initials: M
authors.lastname: Yanagihara
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 Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8522, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8522, Japan.
authors.forename: Syunji
authors.initials: S
authors.lastname: Horie
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: D027241:Amino Acid Transport System y+L / Q000037:antagonists & inhibitors / Q000378:metabolism*; D026921:Amino Acid Transport Systems, Neutral / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000598:Amino Acids, Cyclic / Q000494:pharmacology; D000818:Animals; D003545:Cysteine / Q000378:metabolism / Q000494:pharmacology*; D004032:Diet; D004435:Eating; D004558:Electric Stimulation; D005215:Fasting; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006710:Homocysteine / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D016716:PC12 Cells; D019518:Postprandial Period; D051381:Rats; D013997:Time Factors
chemical_list: D027241:Amino Acid Transport System y+L; D026921:Amino Acid Transport Systems, Neutral; D000598:Amino Acids, Cyclic; D006710:Homocysteine; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D003545:Cysteine; D006862:Hydrogen Sulfide
keywords: Contractility; Hydrogen sulfide; Mouse ileum; System L; l-Cysteine