title: Potential role for ET-2 acting through ETA receptors in experimental colitis in mice.
abstract: OBJECTIVE
  This study attempted to clarify the roles of endothelins and mechanisms associated with ETA/ETBreceptors in mouse models of colitis.
  
  
  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 (ETAreceptor antagonist, 10 mg/kg), A-192621 (ETBreceptor 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. ETAand ETBreceptors 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 ETAreceptors might be a potential target for inflammatory bowel diseases.
authors: Department of Pharmacology, Biological Sciences Center, Federal University of Santa Catarina, Florianopolis, SC, Brazil. rfclaudino@gmail.com.|Department of Pharmacology, Biological Sciences Center, Federal University of Parana, Curitiba, PR, 81531-980, Brazil. rfclaudino@gmail.com.
authors: R F
authors: RF
authors: Claudino
authors: Department of Pharmacology, Biological Sciences Center, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
authors: D F
authors: DF
authors: Leite
authors: Department of Pharmacology, Biological Sciences Center, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
authors: A F
authors: AF
authors: Bento
authors: Department of Pharmacology, Biological Sciences Center, Federal University of Parana, Curitiba, PR, 81531-980, Brazil.
authors: J G
authors: JG
authors: Chichorro
authors: Department of Pharmacology, Biological Sciences Center, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
authors: J B
authors: JB
authors: Calixto
authors: Department of Pharmacology, Biological Sciences Center, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
authors: G A
authors: GA
authors: Rae
mesh_terms: D000818:Animals; D000077868:Atrasentan; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D016264:Dextran Sulfate; D019040:E-Selectin / Q000276:immunology; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D065131:Endothelin B Receptor Antagonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000235:genetics / Q000276:immunology; D019333:Endothelin-2 / Q000235:genetics / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D019007:P-Selectin / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000235:genetics / Q000276:immunology; D044023:Receptor, Endothelin B / Q000235:genetics / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid
chemical_list: C120508:A 192621; D016207:Cytokines; D019040:E-Selectin; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D019333:Endothelin-2; D019007:P-Selectin; D011759:Pyrrolidines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D009195:Peroxidase; D000077868:Atrasentan
keywords: 2,4,6-Trinitrobenzene sulfonic acid; Colitis; Dextran sulfate sodium; Endothelins