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.
OBJECTIVE AND DESIGN: The function of the neurokinin 1 (NK1) receptor was investigated in the DSS-induced mousecolitis 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.
Authors: H Yamamoto; K Morise; K Kusugami; A Furusawa; T Konagaya; Y Nishio; H Kaneko; K Uchida; H Nagai; T Mitsuma; H Nagura Journal: J Gastroenterol Date: 1996-08 Impact factor: 7.527
Authors: Matthias A Engel; Mohammad Khalil; Sonja M Mueller-Tribbensee; Christoph Becker; Winfried L Neuhuber; Markus F Neurath; Peter W Reeh Journal: J Gastroenterol Date: 2011-11-12 Impact factor: 7.527
Authors: L A Dieleman; M J Palmen; H Akol; E Bloemena; A S Peña; S G Meuwissen; E P Van Rees Journal: Clin Exp Immunol Date: 1998-12 Impact factor: 4.330
Authors: D Renzi; P Mantellini; A Calabrò; C Panerai; A Amorosi; I Paladini; G Salvadori; M R Garcea; C Surrenti Journal: Ital J Gastroenterol Hepatol Date: 1998-02
Authors: József Kun; István Szitter; Agnes Kemény; Anikó Perkecz; László Kereskai; Krisztina Pohóczky; Aron Vincze; Szilárd Gódi; Imre Szabó; János Szolcsányi; Erika Pintér; Zsuzsanna Helyes Journal: PLoS One Date: 2014-09-29 Impact factor: 3.240