L-cysteine/d,L-homocysteine-regulated ileum motility via system L and B°,+ transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments

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.