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Potential Role for ET-2 Acting Through ETA Receptors in Experimental Colitis in Mice

R F Claudino, D F Leite, A F Bento, J G Chichorro, J B Calixto, G A Rae

Inflamm Res. 2017 Feb;66(2):141-155.

PMID: 27778057

Abstract:

Objective and design:
This study attempted to clarify the roles of endothelins and mechanisms associated with ETA/ETB receptors in mouse models of colitis.
Materials and methods:
Colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 1.5 mg/animal) or dextran sulfate sodium (DSS, 3%). After colitis establishment, mice received Atrasentan (ETA receptor antagonist, 10 mg/kg), A-192621 (ETB receptor antagonist, 20 mg/kg) or Dexamethasone (1 mg/kg) and several inflammatory parameters were assessed, as well as mRNA levels for ET-1, ET-2 and ET receptors.
Results:
Atrasentan treatment ameliorates TNBS- and DSS-induced colitis. In the TNBS model was observed reduction in macroscopic and microscopic score, colon weight, neutrophil influx, IL-1β, MIP-2 and keratinocyte chemoattractant (KC) levels, inhibition of adhesion molecules expression and restoration of IL-10 levels. However, A192621 treatment did not modify any parameter. ET-1 and ET-2 mRNA was decreased 24 h, but ET-2 mRNA was markedly increased at 48 h after TNBS. ET-2 was able to potentiate LPS-induced KC production in vitro. ETA and ETB receptors mRNA were increased at 24, 48 and 72 h after colitis induction.
Conclusions:
Atrasentan treatment was effective in reducing the severity of colitis in DSS- and TNBS-treated mice, suggesting that ETA receptors might be a potential target for inflammatory bowel diseases.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP195529545 A192621 A192621 195529-54-5 Price
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