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

Eur J Pharmacol. 2015 Oct 5:764:471-479. doi: 10.1016/j.ejphar.2015.07.042. Epub 2015 Jul 19.

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.

Keywords: Contractility; Hydrogen sulfide; Mouse ileum; System L; l-Cysteine.

MeSH terms

  • Amino Acid Transport System y+L / antagonists & inhibitors
  • Amino Acid Transport System y+L / metabolism*
  • Amino Acid Transport Systems, Neutral / antagonists & inhibitors
  • Amino Acid Transport Systems, Neutral / metabolism*
  • Amino Acids, Cyclic / pharmacology
  • Animals
  • Cysteine / metabolism
  • Cysteine / pharmacology*
  • Diet
  • Eating*
  • Electric Stimulation
  • Fasting*
  • Gastrointestinal Motility / drug effects*
  • Homocysteine / pharmacology*
  • Hydrogen Sulfide / metabolism*
  • Ileum / drug effects*
  • Ileum / innervation
  • Ileum / metabolism
  • In Vitro Techniques
  • Male
  • Mice
  • PC12 Cells
  • Postprandial Period
  • Rats
  • Time Factors

Substances

  • Amino Acid Transport System y+L
  • Amino Acid Transport Systems, Neutral
  • Amino Acids, Cyclic
  • Homocysteine
  • 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid
  • Cysteine
  • Hydrogen Sulfide