title: Effects of Food Components That Activate TRPA1 Receptors on Mucosal Ion Transport in the Mouse Intestine.
abstract: TRPA1 is a ligand-activated cation channel found in the intestine and other tissues. Components of food that stimulate TRPA1 receptors (phytonutrients) include allyl isothiocyanate, cinnamaldehyde and linalool, but these may also act at other receptors. Cells lining the intestinal mucosa are immunoreactive for TRPA1 andTrpa1mRNA occurs in mucosal extracts, suggesting that the TRPA1 receptor is the target for these agonists. However, in situ hybridisation revealsTrpa1expression in 5-HT containing enteroendocrine cells, not enterocytes. TRPA1 agonists evoke mucosal secretion, which may be indirect (through release of 5-HT) or direct by activation of enterocytes. We investigated effects of the phytonutrients on transmucosal ion currents in mouse duodenum and colon, and the specificity of the phytonutrients in cells transfected withTrpa1, and inTrpa1-deficient mice. The phytonutrients increased currents in the duodenum with the relative potencies: allyl isothiocyanate (AITC) > cinnamaldehyde > linalool (0.1 to 300 μM). The rank order was similar in the colon, but linalool was ineffective. Responses to AITC were reduced by the TRPA1 antagonist HC-030031 (100 μM), and were greatly diminished inTrpa1-/- duodenum and colon. Responses were not reduced by tetrodotoxin, 5-HT receptor antagonists, or atropine, but inhibition of prostaglandin synthesis reduced responses. Thus, functional TRPA1 channels are expressed by enterocytes of the duodenum and colon. Activation of enterocyte TRPA1 by food components has the potential to facilitate nutrient absorption.
authors.affiliation: Department of Anatomy & Neuroscience, University of Melbourne, Parkville VIC 3010, Australia. l.fothergill@student.unimelb.edu.au.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Fothergill
authors.affiliation: Department of Anatomy & Neuroscience, University of Melbourne, Parkville VIC 3010, Australia. b.callaghan@unimelb.edu.ac.
authors.forename: Brid
authors.initials: B
authors.lastname: Callaghan
authors.affiliation: Department of Anatomy & Neuroscience, University of Melbourne, Parkville VIC 3010, Australia. leni.rivera@deakin.edu.au.|Metabolic Research Unit, School of Medicine, Deakin University, Geelong VIC 3216, Australia. leni.rivera@deakin.edu.au.
authors.forename: Leni R
authors.initials: LR
authors.lastname: Rivera
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville VIC 3052, Australia. Tinamarie.lieu@monash.edu.
authors.forename: TinaMarie
authors.initials: T
authors.lastname: Lieu
authors.affiliation: Department of Anatomy & Neuroscience, University of Melbourne, Parkville VIC 3010, Australia. Daniel.Poole@monash.edu.|Monash Institute of Pharmaceutical Sciences, Monash University, Parkville VIC 3052, Australia. Daniel.Poole@monash.edu.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Poole
authors.affiliation: Biological Optical Microscopy Platform, University of Melbourne, Parkville VIC 3010, Australia. hcho@unimelb.edu.au.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: In Vivo Animal Nutrition & Health, Talhouët, Saint-Nolff 56250, France. david.bravo@pancosma.ch.
authors.forename: David M
authors.initials: DM
authors.lastname: Bravo
authors.affiliation: Department of Anatomy & Neuroscience, University of Melbourne, Parkville VIC 3010, Australia. j.furness@unimelb.edu.au.|Florey Institute of Neuroscience and Mental Health, Parkville VIC 3010, Australia. j.furness@unimelb.edu.au.
authors.forename: John B
authors.initials: JB
authors.lastname: Furness
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000080462:Acyclic Monoterpenes; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003106:Colon / Q000502:physiology; D004386:Duodenum / Q000502:physiology; D055724:Electrophysiological Phenomena; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005502:Food; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000502:physiology*; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039821:Monoterpenes / Q000494:pharmacology; D064209:Phytochemicals / Q000494:pharmacology*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D014162:Transfection; D050051:Transient Receptor Potential Channels / Q000172:deficiency / Q000187:drug effects* / Q000235:genetics
chemical_list: D000080462:Acyclic Monoterpenes; D017879:Isothiocyanates; D039821:Monoterpenes; D064209:Phytochemicals; D058831:Serotonin 5-HT3 Receptor Antagonists; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C041942:2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate; D000171:Acrolein; C018584:linalool; C012843:cinnamaldehyde; D002118:Calcium
keywords: enteroendocrine cells; intestine; micronutrients; serotonin; transepithelial transport; transient receptor potential A1