Title
Involvement of afferent neurons in the pathogenesis of endotoxin-induced ileus in mice: role of CGRP and TRPV1 receptors Involvement of afferent neurons in the pathogenesis of endotoxin-induced ileus in mice: role of CGRP and TRPV1 receptors
Author
Faculty/Department
Administrative Services
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Amsterdam ,
Subject
Pharmacology. Therapy
Source (journal)
European journal of pharmacology. - Amsterdam
Volume/pages
615(2009) :1/3 , p. 177-184
ISSN
0014-2999
ISI
000268218100026
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Activation of neuronal reflex pathways by inflammatory mediators is postulated as an important pathogenic mechanism in postoperative ileus. In this study, we investigated the involvement of afferent neurons and more specifically the role of the transient receptor potential vanilloid receptor type 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in endotoxin-induced motility disturbances in mice. Mice were injected with either lipopolysaccharides (LPS) or saline (control) and pre-treated with hexamethonium (blocker of neuronal transmission), capsaicin (neurotoxin), CGRP 8-37 (CGRP antagonist) or BCTC (TRPV1 receptor antagonist). We measured gastric emptying and intestinal transit of Evans blue next to rectal temperature and a global sickness behaviour scale. In vehicle-treated mice, LPS significantly delayed gastric emptying, small intestinal transit and rectal temperature while the sickness behaviour scale was increased. Hexamethonium, capsaicin, CGRP8-37 and BCTC all reversed the endotoxin-induced delay in gastric emptying and significantly reduced the delay in intestinal transit without effect on the endotoxin-induced decrease in rectal temperature and increase in sickness behaviour scale. Our findings provide evidence for the involvement of afferent nerves in the pathogenesis of endotoxin-induced motility disturbances in mice mediated via CGRP and TRPV1 receptors. Blockade of CGRP and TRPV1 receptors may offer a novel strategy for the treatment of endotoxin-induced ileus.
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