Vanilloid receptor (TRPV1)-deficient mice show increased susceptibility to dinitrobenzene sulfonic acid induced colitis
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In the human colon, vanilloid receptor TRPV1 is overexpressed both in afferent nerve terminals and in epithelial cells during inflammation. In the past years, pharmacological experiments using TRPV1 agonists and antagonists revealed that TRPV1 receptors may play proinflammatory and protective roles in the gastrointestinal tract. Here, we applied a genetic approach to define the role of TRPV1 and analyzed the effects of dinitrobenzene sulfonic acid (DNBS)-induced colitis in TRPV1-deficient (TRPV1−/−) mice. Intrarectal infusion of DNBS induced increased inflammation in TRPV1−/− mice compared to wild-type littermates (TRPV1+/+) as evaluated by macroscopic scoring and myeloperoxidase assays. This finding indicates that TRPV1 receptors are required for the protection within sensory pathways that regulate the response following the initiation of colonic inflammation. Electrophysiological recordings from circular smooth-muscle cells, performed 8 and 24 h after DNBS treatment, revealed strong spontaneous oscillatory action potentials in TRPV1−/− but not in TRPV1+/+ colons, indicating an early TRPV1-mediated control of inflammation-induced irritation of smooth-muscle activities. These unexpected results suggest that TRPV1 receptors mediate endogenous protection against experimentally induced colonic inflammation.
KeywordsVanilloid Gastrointestinal tract Sensory neurons Inflammation Capsaicin
Vanilloid receptor type 1
TRPV1 wild-type littermates
Dinitrobenzene sulfonic acid
Resting membrane potentials
We wish to thank Dr. Peter Holzer for discussions and suggestions on the manuscript and Dr. David Julius for providing the TRPV1 mutant mice. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (LU755/1-3), Förderprogramm für Forschung und Lehre der Medizinischen Fakultät der LMU München (FöFoLe), and by a scholarship from the Hertie Foundation (to B.L.).
- 1.Selve N (1992) Chronic intrajejunal TNBS application in TNBS-sensitized rats: a new model of chronic inflammatory bowel diseases. Agents Actions Spec No:C15–C17Google Scholar
- 3.Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 398:816–824Google Scholar