Tags

Type your tag names separated by a space and hit enter

Role of TRPV1 and TRPA1 in visceral hypersensitivity to colorectal distension during experimental colitis in rats.
Eur J Pharmacol 2013; 698(1-3):404-12EJ

Abstract

The aim of the present study is to investigate the effects of TRPV1 and TRPA1 receptor antagonists and their synergism on the visceromotor responses during experimental colitis in rats. Colitis was induced in rats by a TNBS/ethanol enema at day 0 and was assessed at day 3 using endoscopy, histology and a myeloperoxidase assay. The visceromotor response to colorectal distension (10-80 mmHg) was evaluated in conscious rats before (control condition) and 3 days after 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration (colitis condition). At day 3, visceromotor responses were assessed before and after treatment with a TRPV1 (BCTC) or TRPA1 (TCS-5861528) receptor antagonist either alone or in combination and either after intraperitoneal or intrathecal administration. Endoscopy, microscopy and myeloperoxidase activity indicated severe colonic tissue damage 3 days after TNBS administration. Colorectal distension-evoked visceromotor responses demonstrated a 2.9-fold increase during acute colitis (day 3) compared to control conditions. Intraperitoneal and intrathecal administration of BCTC or TCS-5861528 partially reversed the colitis-induced increase in visceromotor responses compared to control conditions (P<0.05). Intraperitoneal blockade of TRPA1 plus TRPV1 further decreased the enhanced visceromotor responses at high distension pressures (40-80 mmHg) compared to blockade of either TRPV1 or TRPA1 alone. This synergistic effect was not seen after combined intrathecal blockade of TRPA1 plus TRPV1. The present study demonstrates that in the rat, TRPV1 and TRPA1 play a pivotal role in visceral hypersensitivity at the peripheral and spinal cord level during acute TNBS colitis. Target interaction, however, is presumably mediated via a peripheral site of action.

Authors+Show Affiliations

Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.No 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

23099257

Citation

Vermeulen, Wim, et al. "Role of TRPV1 and TRPA1 in Visceral Hypersensitivity to Colorectal Distension During Experimental Colitis in Rats." European Journal of Pharmacology, vol. 698, no. 1-3, 2013, pp. 404-12.
Vermeulen W, De Man JG, De Schepper HU, et al. Role of TRPV1 and TRPA1 in visceral hypersensitivity to colorectal distension during experimental colitis in rats. Eur J Pharmacol. 2013;698(1-3):404-12.
Vermeulen, W., De Man, J. G., De Schepper, H. U., Bult, H., Moreels, T. G., Pelckmans, P. A., & De Winter, B. Y. (2013). Role of TRPV1 and TRPA1 in visceral hypersensitivity to colorectal distension during experimental colitis in rats. European Journal of Pharmacology, 698(1-3), pp. 404-12. doi:10.1016/j.ejphar.2012.10.014.
Vermeulen W, et al. Role of TRPV1 and TRPA1 in Visceral Hypersensitivity to Colorectal Distension During Experimental Colitis in Rats. Eur J Pharmacol. 2013 Jan 5;698(1-3):404-12. PubMed PMID: 23099257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of TRPV1 and TRPA1 in visceral hypersensitivity to colorectal distension during experimental colitis in rats. AU - Vermeulen,Wim, AU - De Man,Joris G, AU - De Schepper,Heiko U, AU - Bult,Hidde, AU - Moreels,Tom G, AU - Pelckmans,Paul A, AU - De Winter,Benedicte Y, Y1 - 2012/10/23/ PY - 2012/06/27/received PY - 2012/10/05/revised PY - 2012/10/13/accepted PY - 2012/10/27/entrez PY - 2012/10/27/pubmed PY - 2013/6/12/medline SP - 404 EP - 12 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 698 IS - 1-3 N2 - The aim of the present study is to investigate the effects of TRPV1 and TRPA1 receptor antagonists and their synergism on the visceromotor responses during experimental colitis in rats. Colitis was induced in rats by a TNBS/ethanol enema at day 0 and was assessed at day 3 using endoscopy, histology and a myeloperoxidase assay. The visceromotor response to colorectal distension (10-80 mmHg) was evaluated in conscious rats before (control condition) and 3 days after 2,4,6-trinitrobenzene sulfonic acid (TNBS) administration (colitis condition). At day 3, visceromotor responses were assessed before and after treatment with a TRPV1 (BCTC) or TRPA1 (TCS-5861528) receptor antagonist either alone or in combination and either after intraperitoneal or intrathecal administration. Endoscopy, microscopy and myeloperoxidase activity indicated severe colonic tissue damage 3 days after TNBS administration. Colorectal distension-evoked visceromotor responses demonstrated a 2.9-fold increase during acute colitis (day 3) compared to control conditions. Intraperitoneal and intrathecal administration of BCTC or TCS-5861528 partially reversed the colitis-induced increase in visceromotor responses compared to control conditions (P<0.05). Intraperitoneal blockade of TRPA1 plus TRPV1 further decreased the enhanced visceromotor responses at high distension pressures (40-80 mmHg) compared to blockade of either TRPV1 or TRPA1 alone. This synergistic effect was not seen after combined intrathecal blockade of TRPA1 plus TRPV1. The present study demonstrates that in the rat, TRPV1 and TRPA1 play a pivotal role in visceral hypersensitivity at the peripheral and spinal cord level during acute TNBS colitis. Target interaction, however, is presumably mediated via a peripheral site of action. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/23099257/Role_of_TRPV1_and_TRPA1_in_visceral_hypersensitivity_to_colorectal_distension_during_experimental_colitis_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(12)00860-6 DB - PRIME DP - Unbound Medicine ER -