Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: B(1) and B(2) receptor antagonists and B(1) receptor knockout mice (B1(-/-) ) were used to assess the involvement of B(1) and B(2) receptor signalling in a DSS- colitis. B(1) receptor, B(2) receptor, occludin and claudin-4 expression, cytokine levels and cell permeability were evaluated in colon from wild-type (WT) and B1(-/-) mice. KEY RESULTS: DSS-induced colitis was significantly exacerbated in B1(-/-) compared with WT mice. IL-1β, IFN-γ, keratinocyte-derived chemokine and macrophage inflammatory protein-2 were markedly increased in the colon from DSS-treated B1(-/-) compared with DSS-treated WT mice. Treatment of WT mice with a selective B(1) receptor antagonist, DALBK or SSR240612, had no effect on DSS-induced colitis. Of note, B(2) receptor mRNA expression was significantly up-regulated in colonic tissue from the B1(-/-) mice after DSS administration. Moreover, treatment with a selective B(2) receptor antagonist prevented the exacerbation of colitis in B1(-/-) mice following DSS administration. The water- or DSS-treated B1(-/-) mice showed a decrease in occludin gene expression, which was partially prevented by the B(2) receptor antagonist. CONCLUSIONS AND IMPLICATIONS: A loss of B(1) receptors markedly exacerbates the severity of DSS-induced colitis in mice. The increased susceptibility of B1(-/-) may be associated with compensatory overexpression of B(2) receptors, which, in turn, modulates tight junction expression.
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Authors | R Marcon, R F Claudino, R C Dutra, A F Bento, E C Schmidt, Z L Bouzon, R Sordi, R L T Morais, J B Pesquero, J B Calixto |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 168
Issue 2
Pg. 389-402
(Jan 2013)
ISSN: 1476-5381 [Electronic] England |
PMID | 22889120
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
Chemical References |
- 2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide
- Bradykinin B1 Receptor Antagonists
- Bradykinin B2 Receptor Antagonists
- Cytokines
- Dioxoles
- Receptor, Bradykinin B1
- Receptor, Bradykinin B2
- Sulfonamides
- bradykinin, Leu(8)-des-Arg(9)-
- icatibant
- Dextran Sulfate
- Peroxidase
- Bradykinin
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Topics |
- Animals
- Bradykinin
(analogs & derivatives, pharmacology)
- Bradykinin B1 Receptor Antagonists
- Bradykinin B2 Receptor Antagonists
- Colitis
(chemically induced, metabolism, pathology)
- Cytokines
(metabolism)
- Dextran Sulfate
- Dioxoles
(pharmacology)
- Homeostasis
- Intestinal Mucosa
(metabolism)
- Intestines
(pathology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Peroxidase
(metabolism)
- Receptor, Bradykinin B1
(genetics, metabolism)
- Receptor, Bradykinin B2
(metabolism)
- Sulfonamides
(pharmacology)
- Tight Junctions
(metabolism)
- Up-Regulation
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