The Ion Channel TRPA1 Is Required for Normal Mechanosensation and Is Modulated by Algesic Stimuli
| Autor: | Christopher M. Martin, Patrick A. Hughes, Andrea M. Harrington, Nicole J. Cooper, B. Adam, David P. Corey, Tracey A. O'Donnell, Grigori Y. Rychkov, L. Ashley Blackshaw, Tobias Liebregts, Kelvin Y. Kwan, Gerald Holtmann, Stuart M. Brierley, Amanda J. Page |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Pathology Action Potentials Pharmacology Distension Mechanotransduction Cellular TRPV Mice Transient receptor potential channel chemistry.chemical_compound Transient Receptor Potential Channels Ganglia Spinal Intestinal Mucosa TRPA1 Cation Channel In Situ Hybridization Pain Measurement Mice Knockout Reverse Transcriptase Polymerase Chain Reaction Chemistry Gastroenterology food and beverages Colitis Immunohistochemistry Stimulation Chemical Neuroanatomical Tract-Tracing Techniques Nociception medicine.anatomical_structure Hyperalgesia Female Nodose Ganglion psychological phenomena and processes medicine.medical_specialty Colon In situ hybridization Bradykinin Splanchnic nerves Article Pelvis Pressure medicine Animals Receptor PAR-2 RNA Messenger Afferent Pathways Hepatology Mechanosensation Splanchnic Nerves Mice Inbred C57BL Disease Models Animal Trinitrobenzenesulfonic Acid Capsaicin |
| Zdroj: | Gastroenterology. 137:2084-2095.e3 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2009.07.048 |
| Popis: | BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: TRPA1 is required for normal mechanoand 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. CONCLUSIONS: These findings demonstrate a previously unrecognized role for TRPA1 in normal and inflamed mechanosensory function and nociception within the viscera. |
| Databáze: | OpenAIRE |
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