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TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats.
Am J Physiol Gastrointest Liver Physiol. 2008 Jan; 294(1):G245-53.AJ

Abstract

Rats with experimental colitis suffer from impaired gastric emptying (GE). We previously showed that this phenomenon involves afferent neurons within the pelvic nerve. In this study, we aimed to identify the mediators involved in this afferent hyperactivation. Colitis was induced by trinitrobenzene sulfate (TNBS) instillation. We determined GE, distal front, and geometric center (GC) of intestinal transit 30 min after intragastric administration of a semiliquid Evans blue solution. We evaluated the effects of the transient receptor potential vanilloid type 1 (TRPV1) antagonists capsazepine (5-10 mg/kg) and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)carboxamide (BCTC; 1-10 mg/kg) and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (150 microg/kg). To determine TRPV1 receptor antagonist sensitivity, we examined their effect on capsaicin-induced relaxations of isolated gastric fundus muscle strips. Immunocytochemical staining of TRPV1 and RT-PCR analysis of TRPV1 mRNA were performed in dorsal root ganglion (DRG) L6-S1. TNBS-induced colitis reduced GE but had no effect on intestinal motility. Capsazepine reduced GE in controls but had no effect in rats with colitis. At doses that had no effects in controls, BCTC and CGRP-(8-37) significantly improved colitis-induced gastroparesis. Capsazepine inhibited capsaicin-induced relaxations by 35% whereas BCTC completely abolished them. TNBS-induced colitis increased TRPV1-like immunoreactivity and TRPV1 mRNA content in pelvic afferent neuronal cell bodies in DRG L6-S1. In conclusion, distal colitis in rats impairs GE via sensitized pelvic afferent neurons. We provided pharmacological, immunocytochemical, and molecular biological evidence that this sensitization is mediated by TRPV1 receptors and involves CGRP release.

Authors+Show Affiliations

Laboratory of Gastroenterology, Faculty of Medicine, Univ. of Antwerp, Universiteitsplein 1, 2610 Antwerp (Belgium benedicte.dewinter@ua.ac.be).No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17991707

Citation

De Schepper, H U., et al. "TRPV1 Receptor Signaling Mediates Afferent Nerve Sensitization During Colitis-induced Motility Disorders in Rats." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 294, no. 1, 2008, pp. G245-53.
De Schepper HU, De Man JG, Ruyssers NE, et al. TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats. Am J Physiol Gastrointest Liver Physiol. 2008;294(1):G245-53.
De Schepper, H. U., De Man, J. G., Ruyssers, N. E., Deiteren, A., Van Nassauw, L., Timmermans, J. P., Martinet, W., Herman, A. G., Pelckmans, P. A., & De Winter, B. Y. (2008). TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats. American Journal of Physiology. Gastrointestinal and Liver Physiology, 294(1), G245-53.
De Schepper HU, et al. TRPV1 Receptor Signaling Mediates Afferent Nerve Sensitization During Colitis-induced Motility Disorders in Rats. Am J Physiol Gastrointest Liver Physiol. 2008;294(1):G245-53. PubMed PMID: 17991707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats. AU - De Schepper,H U, AU - De Man,J G, AU - Ruyssers,N E, AU - Deiteren,A, AU - Van Nassauw,L, AU - Timmermans,J-P, AU - Martinet,W, AU - Herman,A G, AU - Pelckmans,P A, AU - De Winter,B Y, Y1 - 2007/11/08/ PY - 2007/11/10/pubmed PY - 2008/2/22/medline PY - 2007/11/10/entrez SP - G245 EP - 53 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am. J. Physiol. Gastrointest. Liver Physiol. VL - 294 IS - 1 N2 - Rats with experimental colitis suffer from impaired gastric emptying (GE). We previously showed that this phenomenon involves afferent neurons within the pelvic nerve. In this study, we aimed to identify the mediators involved in this afferent hyperactivation. Colitis was induced by trinitrobenzene sulfate (TNBS) instillation. We determined GE, distal front, and geometric center (GC) of intestinal transit 30 min after intragastric administration of a semiliquid Evans blue solution. We evaluated the effects of the transient receptor potential vanilloid type 1 (TRPV1) antagonists capsazepine (5-10 mg/kg) and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)carboxamide (BCTC; 1-10 mg/kg) and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (150 microg/kg). To determine TRPV1 receptor antagonist sensitivity, we examined their effect on capsaicin-induced relaxations of isolated gastric fundus muscle strips. Immunocytochemical staining of TRPV1 and RT-PCR analysis of TRPV1 mRNA were performed in dorsal root ganglion (DRG) L6-S1. TNBS-induced colitis reduced GE but had no effect on intestinal motility. Capsazepine reduced GE in controls but had no effect in rats with colitis. At doses that had no effects in controls, BCTC and CGRP-(8-37) significantly improved colitis-induced gastroparesis. Capsazepine inhibited capsaicin-induced relaxations by 35% whereas BCTC completely abolished them. TNBS-induced colitis increased TRPV1-like immunoreactivity and TRPV1 mRNA content in pelvic afferent neuronal cell bodies in DRG L6-S1. In conclusion, distal colitis in rats impairs GE via sensitized pelvic afferent neurons. We provided pharmacological, immunocytochemical, and molecular biological evidence that this sensitization is mediated by TRPV1 receptors and involves CGRP release. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/17991707/TRPV1_receptor_signaling_mediates_afferent_nerve_sensitization_during_colitis_induced_motility_disorders_in_rats_ L2 - http://www.physiology.org/doi/full/10.1152/ajpgi.00351.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -