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Journal of Molecular Medicine

, Volume 84, Issue 2, pp 142–146 | Cite as

Vanilloid receptor (TRPV1)-deficient mice show increased susceptibility to dinitrobenzene sulfonic acid induced colitis

  • F. Massa
  • A. Sibaev
  • G. Marsicano
  • H. Blaudzun
  • M. Storr
  • B. LutzEmail author
Rapid Communication

Abstract

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.

Keywords

Vanilloid Gastrointestinal tract Sensory neurons Inflammation Capsaicin 

Abbreviations

TRPV1

Vanilloid receptor type 1

TRPV1−/−

TRPV1-deficient mice

TRPV1+/+

TRPV1 wild-type littermates

DNBS

Dinitrobenzene sulfonic acid

MPO

Myeloperoxidase

RMP

Resting membrane potentials

Notes

Acknowledgements

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.).

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • F. Massa
    • 1
    • 2
  • A. Sibaev
    • 3
  • G. Marsicano
    • 1
    • 2
  • H. Blaudzun
    • 2
  • M. Storr
    • 3
  • B. Lutz
    • 1
    • 2
    Email author
  1. 1.Department of Physiological ChemistryJohannes Gutenberg-University MainzMainzGermany
  2. 2.Molecular Genetics of BehaviourMax Planck Institute of PsychiatryMunichGermany
  3. 3.II Medical Department, Klinikum GrosshadernLudwig-Maximilians University of MunichMunichGermany

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