| Nociceptin/orphanin FQ inhibition with SB612111 ameliorates dextran sodium sulfate-induced colitis. | |
| | |
MedLine Citation:
|
PMID: 22449384 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Inflammatory bowel diseases, primarily Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract with unknown etiology. The majority of current therapeutic agents focus on controlling proinflammatory molecules. The neuropeptide nociceptin/orphanin FQ (N/OFQ) has been described as a potential immunomodulator for inflammatory bowel diseases. In this study, we asked whether the small molecule N/OFQ antagonist (-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB612111) would inhibit the development of dextran sodium sulfate-induced colitis in C57BL/6 mice. Inhibition of the N/OFQ receptor (NOP) by SB612111 significantly ameliorated the clinical disease course in these animals, as indicated by reduced fecal bleeding, improved recovery from diarrhea and weight loss, and a reduction in histopathological alterations. In addition, the inflammatory response in the colon was diminished, as demonstrated by reduced cytokine protein and messenger RNA expression for CXCL1/keratinocyte-derived chemokine, interferon-γ, interleukin-1β, interleukin-6, and tumor necrosis factor-α, some of which are known targets for the treatment of this devastating disease. Our results strongly support a role for the receptor-ligand pair NOP-N/OFQ in the pathogenesis of colitis. We conclude that inhibition of NOP receptors with small molecule inhibitors may constitute a novel, urgently needed approach for the treatment of inflammatory bowel diseases. |
| | |
Authors:
|
Carsten Alt; Jennifer Lam; Travis Harrison; Kathleen M Kershaw; Steven Samuelsson; Lawrence Toll; Annalisa D'Andrea |
Related Documents
:
|
7803264 - Acute lymphoblastic leukaemia in adults: the case for a strategic shift in study approach. 21044454 - Use of methotrexate in adult-onset still's disease. 22152294 - Epidemiological simulation modeling and spatial analysis for foot-and-mouth disease con... 494034 - Rheumatoid arthritic syndrome after chikungunya fever. 6333094 - Babesiosis in asplenic hosts. 21586324 - Putative roles of cilia in polycystic kidney disease. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-3-16 |
Journal Detail:
|
Title: European journal of pharmacology Volume: - ISSN: 1879-0712 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
|
Created Date: 2012-3-27 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2012. Published by Elsevier B.V. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Adenosine A(1) receptors do not play a major role in the regulation of lipogenic gene expression in ...
Next Document: First and second generation H(1) histamine receptor antagonists produce different sleep-inducing pro...