Inflammation Research

, Volume 63, Issue 5, pp 399–409

Role of neurokinin 1 receptors in dextran sulfate-induced colitis: studies with gene-deleted mice and the selective receptor antagonist netupitant

  • István Szitter
  • Erika Pintér
  • Anikó Perkecz
  • Ágnes Kemény
  • József Kun
  • László Kereskai
  • Claudio Pietra
  • John P. Quinn
  • Andreas Zimmer
  • Alexandra Berger
  • Christopher J. Paige
  • Zsuzsanna Helyes
Original Research Paper

DOI: 10.1007/s00011-014-0712-x

Cite this article as:
Szitter, I., Pintér, E., Perkecz, A. et al. Inflamm. Res. (2014) 63: 399. doi:10.1007/s00011-014-0712-x

Abstract

Objective and design

The function of the neurokinin 1 (NK1) receptor was investigated in the DSS-induced mouse colitis model using NK1 receptor-deficient mice and the selective antagonist netupitant.

Subjects

Colitis was induced by oral administration of 20 mg/ml DSS solution for 7 days in C57BL/6 and Tacr1 KO animals (n = 5–7).

Treatment

During the induction, one-half of the C57BL/6 and Tacr1 KO group received one daily dose of 6 mg/kg netupitant, administered intraperitoneally, the other half of the group received saline, respectively.

Methods

Disease activity index (DAI), on the basis of stool consistency, blood and weight loss, was determined over 7 days. Histological evaluation, myeloperoxidase (MPO) measurement, cytokine concentrations and receptor expression analysis were performed on the colon samples.

Results

NK1 receptors are up-regulated in the colon in response to DSS treatment. DSS increased DAI, histopathological scores, BLC, sICAM-1, IFN-γ, IL-16 and JE in wildtype mice, which were significantly reduced in NK1 receptor-deficient ones. NK1 receptor antagonism with netupitant significantly diminished DAI, inflammatory histopathological alterations, BLC, IFN-γ, IL-13 and IL-16 in wildtype mice, but not in the NK1-deficient ones. MPO was similarly elevated and netupitant significantly decreased its activity in both groups.

Conclusions

NK1 receptor antagonism could be beneficial for colitis via inhibiting different inflammatory mechanisms.

Keywords

Neurogenic inflammation Tachykinins Inflammatory bowel disease Edema NK1 receptor antagonist 

Copyright information

© Springer Basel 2014

Authors and Affiliations

  • István Szitter
    • 1
    • 2
  • Erika Pintér
    • 1
    • 2
    • 3
  • Anikó Perkecz
    • 1
    • 2
  • Ágnes Kemény
    • 1
    • 2
  • József Kun
    • 1
    • 2
  • László Kereskai
    • 4
  • Claudio Pietra
    • 5
  • John P. Quinn
    • 6
  • Andreas Zimmer
    • 7
  • Alexandra Berger
    • 8
    • 9
  • Christopher J. Paige
    • 8
    • 9
  • Zsuzsanna Helyes
    • 1
    • 2
    • 3
  1. 1.Department of Pharmacology and PharmacotherapyUniversity of PécsPécsHungary
  2. 2.János Szentágothai Research CentrePécsHungary
  3. 3.PharmInVivo Ltd.PécsHungary
  4. 4.Department of PathologyUniversity of PécsPécsHungary
  5. 5.Helsinn Healthcare SA, Preclinical R&DLuganoSwitzerland
  6. 6.Department of Molecular and Clinical Pharmacology, Institute of TranslationUniversity of Liverpool, Liverpool UniversityLiverpoolUK
  7. 7.Institute of Molecular PsychiatryUniversity of BonnBonnGermany
  8. 8.Ontario Cancer InstituteUniversity Health NetworkTorontoCanada
  9. 9.Department of ImmunologyUniversity of TorontoTorontoCanada

Personalised recommendations