Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/58287
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dc.contributor.authorBrierley, S.en
dc.contributor.authorHughes, P.en
dc.contributor.authorPage, A.en
dc.contributor.authorKwan, K.en
dc.contributor.authorMartin, C.en
dc.contributor.authorO'Donnell, T.en
dc.contributor.authorIsaacs, N.en
dc.contributor.authorHarrington, A.en
dc.contributor.authorAdam, B.en
dc.contributor.authorLiebregts, T.en
dc.contributor.authorHoltmann, G.en
dc.contributor.authorCorey, D.en
dc.contributor.authorRychkov, G.en
dc.contributor.authorBlackshaw, L.en
dc.date.issued2009en
dc.identifier.citationGastroenterology, 2009; 137(6):2084-2095en
dc.identifier.issn0016-5085en
dc.identifier.issn1528-0012en
dc.identifier.urihttp://hdl.handle.net/2440/58287-
dc.description.abstract<h4>Background & aims</h4>The transient receptor potential (TRP) channel family includes transducers of mechanical and chemical stimuli for visceral sensory neurons. TRP ankyrin 1 (TRPA1) is implicated in inflammatory pain; it interacts with G-protein-coupled receptors, but little is known about its role in the gastrointestinal (GI) tract. Sensory information from the GI tract is conducted via 5 afferent subtypes along 3 pathways.<h4>Methods</h4>Nodose and dorsal root ganglia whose neurons innnervate 3 different regions of the GI tract were analyzed from wild-type and TRPA1(-/-) mice using quantitative reverse-transcription polymerase chain reaction, retrograde labeling, and in situ hybridization. Distal colon sections were analyzed by immunohistochemistry. In vitro electrophysiology and pharmacology studies were performed, and colorectal distension and visceromotor responses were measured. Colitis was induced by administration of trinitrobenzene sulphonic acid.<h4>Results</h4>TRPA1 is required for normal mechano- and chemosensory function in specific subsets of vagal, splanchnic, and pelvic afferents. The behavioral responses to noxious colonic distension were substantially reduced in TRPA1(-/-) mice. TRPA1 agonists caused mechanical hypersensitivity, which increased in mice with colitis. Colonic afferents were activated by bradykinin and capsaicin, which mimic effects of tissue damage; wild-type and TRPA1(-/-) mice had similar direct responses to these 2 stimuli. After activation by bradykinin, wild-type afferents had increased mechanosensitivity, whereas, after capsaicin exposure, mechanosensitivity was reduced: these changes were absent in TRPA1(-/-) mice. No interaction between protease-activated receptor-2 and TRPA1 was evident.<h4>Conclusions</h4>These findings demonstrate a previously unrecognized role for TRPA1 in normal and inflamed mechanosensory function and nociception within the viscera.en
dc.description.statementofresponsibilityStuart M. Brierley, Patrick A. Hughes, Amanda J. Page, Kelvin Y. Kwan, Christopher M. Martin, Tracey A. O'Donnell, Nicole J. Cooper, Andrea M. Harrington, Birgit Adam, Tobias Liebregts, Gerald Holtmann, David P. Corey, Grigori Y. Rychkov and L. Ashley Blackshawen
dc.language.isoenen
dc.publisherW B Saunders Coen
dc.rightsCopyright © 2009 AGA Institute. Published by Elsevier Inc.en
dc.subjectPelvis; Intestinal Mucosa; Colon; Ganglia, Spinal; Nodose Ganglion; Afferent Pathways; Splanchnic Nerves; Animals; Mice, Inbred C57BL; Mice, Knockout; Mice; Colitis; Hyperalgesia; Disease Models, Animal; Trinitrobenzenesulfonic Acid; Capsaicin; Bradykinin; Receptor, PAR-2; RNA, Messenger; Pain Measurement; Immunohistochemistry; In Situ Hybridization; Reverse Transcriptase Polymerase Chain Reaction; Mechanotransduction, Cellular; Action Potentials; Stimulation, Chemical; Pressure; Female; Male; Transient Receptor Potential Channels; Neuroanatomical Tract-Tracing Techniques; TRPA1 Cation Channelen
dc.titleThe ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimulien
dc.typeJournal articleen
dc.identifier.rmid0020094266en
dc.identifier.doi10.1053/j.gastro.2009.07.048en
dc.identifier.pubid36443-
pubs.library.collectionMolecular and Biomedical Science publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidBrierley, S. [0000-0002-2527-2905]en
dc.identifier.orcidHughes, P. [0000-0001-7324-3626]en
dc.identifier.orcidPage, A. [0000-0002-7086-5865]en
dc.identifier.orcidHarrington, A. [0000-0002-1562-4137]en
dc.identifier.orcidRychkov, G. [0000-0002-2788-2977]en
dc.identifier.orcidBlackshaw, L. [0000-0003-1565-0850]en
Appears in Collections:Molecular and Biomedical Science publications

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