title: Modulation of mouse gastrointestinal motility by allyl isothiocyanate, a constituent of cruciferous vegetables (Brassicaceae): evidence for TRPA1-independent effects.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II, Naples, ItalyInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, National Research Council, Pozzuoli (NA), Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capasso
authors.affiliation: Department of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II, Naples, ItalyInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, National Research Council, Pozzuoli (NA), Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Aviello
authors.affiliation: Department of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II, Naples, ItalyInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, National Research Council, Pozzuoli (NA), Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Romano
authors.affiliation: Department of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II, Naples, ItalyInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, National Research Council, Pozzuoli (NA), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Borrelli
authors.affiliation: Department of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II, Naples, ItalyInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, National Research Council, Pozzuoli (NA), Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: De Petrocellis
authors.affiliation: Department of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II, Naples, ItalyInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, National Research Council, Pozzuoli (NA), Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Department of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II, Naples, ItalyInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, National Research Council, Pozzuoli (NA), Italy.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
mesh_terms: D000818:Animals; D019607:Brassicaceae; D003106:Colon / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000502:physiology; D014675:Vegetables
chemical_list: D017879:Isothiocyanates; D010276:Parasympatholytics; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C004471:allyl isothiocyanate