Modulation of mouse gastrointestinal motility by allyl isothiocyanate, a constituent of cruciferous vegetables (Brassicaceae): evidence for TRPA1-independent effects

Raffaele Capasso, Gabriella Aviello, Barbara Romano, Francesca Borrelli, Luciano De Petrocellis, Vincenzo Di Marzo, Angelo A Izzo

Research output: Contribution to journalArticle

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Abstract

BACKGROUND AND PURPOSE: Allyl isothiocyanate (AITC, mustard oil), a constituent of many common cruciferous vegetables (Brassicaceae), activates transient receptor potential of ankyrin type-1 (TRPA1) channels, claimed to regulate gastrointestinal contractility. In this study, we have investigated the effect of AITC on intestinal motility.

EXPERIMENTAL APPROACH: Effects of AITC were investigated in vivo on upper gastrointestinal transit in mice and in mouse isolated ileum [contractions induced by electrical field stimulation (EFS), acetylcholine and spontaneous contractility]. The contractor activity of AITC was studied in mouse isolated colon. The ability of TRPA1 channel antagonists to block AITC-induced elevation of intracellular Ca(2+) [Ca(2+)](i) was assessed in HEK293 cells transfected with rat TRPA1 channels.

KEY RESULTS: AITC increased [Ca(2+)](i) in HEK293 cells, reduced ileal contractility (acetylcholine-, EFS-induced contractions and spontaneous contractility), but contracted the isolated colon. Gentamicin and camphor (non-selective TRPA1 channel antagonists), HC-030031 and AP18 (selective TRPA1 channel agonists) inhibited AITC-induced effects in HEK293 cells but not in the ileum or colon. AITC-induced contractions were reduced by tetrodotoxin and strongly reduced by nifedipine, cyclopiazonic acid and ryanodine. In vivo, AITC reduced (following i.p. administration) or increased (following intragastric administration) upper gastrointestinal transit in mice These effects were not affected by HC-030031.

CONCLUSION AND IMPLICATIONS: AITC, depending, in vitro, on the regions of gut examined and, in vivo, on the route of administration, exerted both stimulatory and inhibitory effects on intestinal motility, which were not sensitive to TRPA1 channel antagonists. The proposition that TRPA1 channels are the primary targets for AITC to induce contraction should be revised.

Original languageEnglish
Pages (from-to)1966-1977
Number of pages12
JournalBritish Journal of Pharmacology
Volume165
Issue number6
DOIs
Publication statusPublished - Mar 2012

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Ankyrins
Brassicaceae
Gastrointestinal Motility
Vegetables
HEK293 Cells
Gastrointestinal Transit
Colon
Ileum
Electric Stimulation
Acetylcholine
allyl isothiocyanate
2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate
Camphor
Ryanodine
Tetrodotoxin
Nifedipine
Gentamicins

Keywords

  • Animals
  • Brassicaceae
  • Colon
  • Gastrointestinal Motility
  • HEK293 Cells
  • Humans
  • Ileum
  • In Vitro Techniques
  • Isothiocyanates
  • Male
  • Mice
  • Mice, Inbred ICR
  • Muscle Contraction
  • Parasympatholytics
  • Transient Receptor Potential Channels
  • Vegetables
  • Journal Article

Cite this

Modulation of mouse gastrointestinal motility by allyl isothiocyanate, a constituent of cruciferous vegetables (Brassicaceae) : evidence for TRPA1-independent effects. / Capasso, Raffaele; Aviello, Gabriella; Romano, Barbara; Borrelli, Francesca; De Petrocellis, Luciano; Di Marzo, Vincenzo; Izzo, Angelo A.

In: British Journal of Pharmacology, Vol. 165, No. 6, 03.2012, p. 1966-1977.

Research output: Contribution to journalArticle

Capasso, Raffaele ; Aviello, Gabriella ; Romano, Barbara ; Borrelli, Francesca ; De Petrocellis, Luciano ; Di Marzo, Vincenzo ; Izzo, Angelo A. / Modulation of mouse gastrointestinal motility by allyl isothiocyanate, a constituent of cruciferous vegetables (Brassicaceae) : evidence for TRPA1-independent effects. In: British Journal of Pharmacology. 2012 ; Vol. 165, No. 6. pp. 1966-1977.
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AB - BACKGROUND AND PURPOSE: Allyl isothiocyanate (AITC, mustard oil), a constituent of many common cruciferous vegetables (Brassicaceae), activates transient receptor potential of ankyrin type-1 (TRPA1) channels, claimed to regulate gastrointestinal contractility. In this study, we have investigated the effect of AITC on intestinal motility.EXPERIMENTAL APPROACH: Effects of AITC were investigated in vivo on upper gastrointestinal transit in mice and in mouse isolated ileum [contractions induced by electrical field stimulation (EFS), acetylcholine and spontaneous contractility]. The contractor activity of AITC was studied in mouse isolated colon. The ability of TRPA1 channel antagonists to block AITC-induced elevation of intracellular Ca(2+) [Ca(2+)](i) was assessed in HEK293 cells transfected with rat TRPA1 channels.KEY RESULTS: AITC increased [Ca(2+)](i) in HEK293 cells, reduced ileal contractility (acetylcholine-, EFS-induced contractions and spontaneous contractility), but contracted the isolated colon. Gentamicin and camphor (non-selective TRPA1 channel antagonists), HC-030031 and AP18 (selective TRPA1 channel agonists) inhibited AITC-induced effects in HEK293 cells but not in the ileum or colon. AITC-induced contractions were reduced by tetrodotoxin and strongly reduced by nifedipine, cyclopiazonic acid and ryanodine. In vivo, AITC reduced (following i.p. administration) or increased (following intragastric administration) upper gastrointestinal transit in mice These effects were not affected by HC-030031.CONCLUSION AND IMPLICATIONS: AITC, depending, in vitro, on the regions of gut examined and, in vivo, on the route of administration, exerted both stimulatory and inhibitory effects on intestinal motility, which were not sensitive to TRPA1 channel antagonists. The proposition that TRPA1 channels are the primary targets for AITC to induce contraction should be revised.

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KW - Mice, Inbred ICR

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KW - Parasympatholytics

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