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

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.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

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

References

  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–C17
  2. Lomax AE, Fernandez E, Sharkey KA (2005) Plasticity of the enteric nervous system during intestinal inflammation. Neurogastroenterol Motil 17:4–15
    Article PubMed CAS Google 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 398:816–824
    Google Scholar
  4. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543
    Article PubMed CAS Google Scholar
  5. Ward SM, Bayguinov J, Won KJ, Grundy D, Berthoud HR (2003) Distribution of the vanilloid receptor (VR1) in the gastrointestinal tract. J Comp Neurol 465:121–135
    Article PubMed Google Scholar
  6. Tang HB, Inoue A, Oshita K, Nakata Y (2004) Sensitization of vanilloid receptor 1 induced by bradykinin via the activation of second messenger signaling cascades in rat primary afferent neurons. Eur J Pharmacol 498:37–43
    Article PubMed CAS Google Scholar
  7. Kihara N, de la Fuente SG, Fujino K, Takahashi T, Pappas TN, Mantyh CR (2003) Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats. Gut 52:713–719
    Article PubMed CAS Google Scholar
  8. Kimball ES, Wallace NH, Schneider CR, D'Andrea MR, Hornby PJ (2004) Vanilloid receptor 1 antagonists attenuate disease severity in dextran sulphate sodium-induced colitis in mice. Neurogastroenterol Motil 16:811–818
    Article PubMed CAS Google Scholar
  9. Fujino K, Takami Y, de la Fuente SG, Ludwig KA, Mantyh CR (2004) Inhibition of the vanilloid receptor subtype-1 attenuates TNBS-colitis. J Gastrointest Surg 8:842–847
    Article PubMed Google Scholar
  10. Goso C, Evangelista S, Tramontana M, Manzini S, Blumberg PM, Szallasi A (1993) Topical capsaicin administration protects against trinitrobenzene sulfonic acid-induced colitis in the rat. Eur J Pharmacol 249:185–190
    Article PubMed CAS Google Scholar
  11. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313
    Article PubMed CAS Google Scholar
  12. Massa F, Marsicano G, Hermann H, Cannich A, Monory K, Cravatt BF, Ferri GL, Sibaev A, Storr M, Lutz B (2004) The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest 113:1202–1209
    Article PubMed CAS Google Scholar
  13. McVey DC, Vigna SR (2001) The capsaicin VR1 receptor mediates substance P release in toxin A-induced enteritis in rats. Peptides 22:1439–1446
    Article PubMed CAS Google Scholar
  14. Geppetti P, Trevisani M (2004) Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function. Br J Pharmacol 141:1313–1320
    Article PubMed CAS Google Scholar
  15. Menendez L, Lastra A, Hidalgo A, Baamonde A (2004) The analgesic effect induced by capsaicin is enhanced in inflammatory states. Life Sci 74:3235–3244
    Article PubMed CAS Google Scholar
  16. McVey DC, Schmid PC, Schmid HH, Vigna SR (2003) Endocannabinoids induce ileitis in rats via the capsaicin receptor (VR1). J Pharmacol Exp Ther 304:713–722
    Article PubMed CAS Google Scholar
  17. Fujimoto S, Mori M (2004) Characterization of capsaicin-induced, capsazepine-insensitive relaxation of ileal smooth muscle of rats. Eur J Pharmacol 487:175–182
    Article PubMed CAS Google Scholar
  18. Ray AM, Benham CD, Roberts JC, Gill CH, Lanneau C, Gitterman DP, Harries M, Davis JB, Davies CH (2003) Capsazepine protects against neuronal injury caused by oxygen glucose deprivation by inhibiting I(h). J Neurosci 23:10146–10153
    PubMed CAS Google Scholar
  19. Nocerino E, Izzo AA, Borrelli F, Capasso F, Capasso R, Pinto A, Sautebin L, Mascolo N (2002) Relaxant effect of capsazepine in the isolated rat ileum. Naunyn Schmiedebergs Arch Pharmacol 365:187–192
    Article PubMed CAS Google Scholar
  20. Liu L, Simon SA (1997) Capsazepine, a vanilloid receptor antagonist, inhibits nicotinic acetylcholine receptors in rat trigeminal ganglia. Neurosci Lett 228:29–32
    Article PubMed CAS Google Scholar
  21. Docherty RJ, Yeats JC, Piper AS (1997) Capsazepine block of voltage-activated calcium channels in adult rat dorsal root ganglion neurones in culture. Br J Pharmacol 121:1461–1467
    Article PubMed CAS Google Scholar
  22. Horie S, Yamamoto H, Michael GJ, Uchida M, Belai A, Watanabe K, Priestley JV, Murayama T (2004) Protective role of vanilloid receptor type 1 in HCl-induced gastric mucosal lesions in rats. Scand J Gastroenterol 39:303–312
    Article PubMed CAS Google Scholar
  23. Costa B, Giagnoni G, Franke C, Trovato AE, Colleoni M (2004) Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. Br J Pharmacol 143:247–250
    Article PubMed CAS Google Scholar
  24. Linden DR, Sharkey KA, Mawe GM (2003) Enhanced excitability of myenteric AH neurones in the inflamed guinea-pig distal colon. J Physiol 547:589–601
    Article PubMed CAS Google Scholar
  25. Holzer P, Holzer-Petsche U (1997) Tachykinins in the gut. Part II. Roles in neural excitation, secretion and inflammation. Pharmacol Ther 73:219–263
    Article PubMed CAS Google Scholar
  26. Van der Stelt M, Di Marzo V (2004) Endovanilloids. Putative endogenous ligands of transient receptor potential vanilloid 1 channels. Eur J Biochem 271:1827–1834
    Article Google Scholar
  27. Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V, Julius D, Hogestatt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457
    Article PubMed CAS Google Scholar
  28. Cravatt BF, Lichtman AH (2002) The enzymatic inactivation of the fatty acid amide class of signaling lipids. Chem Phys Lipids 121:135–148
    Article PubMed CAS Google Scholar

Download references

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.).

Author information

Authors and Affiliations

  1. Department of Physiological Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 6, 55099, Mainz, Germany
    F. Massa, G. Marsicano & B. Lutz
  2. Molecular Genetics of Behaviour, Max Planck Institute of Psychiatry, 80804, Munich, Germany
    F. Massa, G. Marsicano, H. Blaudzun & B. Lutz
  3. II Medical Department, Klinikum Grosshadern, Ludwig-Maximilians University of Munich, 81377, Munich, Germany
    A. Sibaev & M. Storr

Authors

  1. F. Massa
    You can also search for this author inPubMed Google Scholar
  2. A. Sibaev
    You can also search for this author inPubMed Google Scholar
  3. G. Marsicano
    You can also search for this author inPubMed Google Scholar
  4. H. Blaudzun
    You can also search for this author inPubMed Google Scholar
  5. M. Storr
    You can also search for this author inPubMed Google Scholar
  6. B. Lutz
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toB. Lutz.

Rights and permissions

About this article

Cite this article

Massa, F., Sibaev, A., Marsicano, G. et al. Vanilloid receptor (TRPV1)-deficient mice show increased susceptibility to dinitrobenzene sulfonic acid induced colitis.J Mol Med 84, 142–146 (2006). https://doi.org/10.1007/s00109-005-0016-2

Download citation

Keywords