fr-173657 has been researched along with Colitis* in 2 studies
2 other study(ies) available for fr-173657 and Colitis
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Pharmacological and biochemical characterization of bradykinin B2 receptors in the mouse colon: influence of the TNBS-induced colitis.
This study analyzed bradykinin (BK)-evoked contractile responses in the mouse colon under normal and inflammatory conditions. BK and the preferential B(2) receptor agonists Hyp(3)-BK, Lys-BK, Met-Lys-BK and Tyr(8)-BK produced a marked and concentration-related contraction of the normal mouse colon, whereas the selective B(1) receptor agonist des-Arg(9)-BK had no effect. BK-induced contraction was concentration-dependently antagonized (in a non-competitive manner) by both B(2) receptor antagonists Hoe 140 and FR173657, but not the B(1) receptor antagonist des-Arg(9)-[Leu(8)]-BK. Analysis of the possible mechanisms implicated in the contractile responses of BK in the mouse colon revealed the involvement of the neural release of acetylcholine, the activation of L- and N-type voltage-gated calcium channels, and the release of neuropeptides, prostanoids and leukotrienes. The contraction induced by BK was markedly increased in preparations obtained from TNBS-treated mice. The up-regulation of B(2) receptors following the induction of colitis was confirmed with binding studies using [(3)H]-BK, which revealed a marked increase in B(2) receptor densities, without alterations of affinity. We provide convincing evidence on the relevance of B(2) receptors in the mouse colon under normal conditions, as well as under an inflammatory profile of colitis. Selective B(2) receptor antagonists might well represent rational therapeutic options for treating inflammatory bowel diseases. Topics: Acetylcholine; Animals; Bradykinin; Bradykinin B2 Receptor Antagonists; Calcium Channels, L-Type; Calcium Channels, N-Type; Colitis; Colon; Dose-Response Relationship, Drug; Kallidin; Leukotrienes; Male; Mice; Muscle Contraction; Neuropeptides; Prostaglandins; Quinolines; Receptor, Bradykinin B2; Trinitrobenzenesulfonic Acid | 2007 |
Suppression of dextran sulfate sodium-induced colitis in kininogen-deficient rats and non-peptide B2 receptor antagonist-treated rats.
Various proinflammatory mediators are believed to be involved in the processes and symptoms of ulcerative colitis (UC). To determine whether endogenous kinin enhances the severity of UC, we induced experimental colitis (EC) in kininogen-deficient mutant rats and tested the effect of a non-peptide B2 receptor antagonist. EC was induced in male kininogen-deficient Brown Norway-Katholiek rats (BN-Ka) and normal Brown Norway-Kitasato rats (BN-Ki) with 5% dextran sulfate sodium (DSS). Sprague-Dawley rats (SD) were also used. Colon length, body weight and hematocrit were determined for 7 days. Effects of FR173657, an orally active B2 antagonist, were tested. The colon length was shortened in BN-Ki with DSS treatment, but not in BN-Ka, and the difference between their lengths was significant. The hematocrit value was also reduced in BN-Ki, and the difference in hematocrit between BN-Ki and BN-Ka was significant. In SD, shortening of the colon and reduction in hematocrit were also observable, and both were blunted by FR173657. The survival rate in SD given DSS for 7 days was 68%, but FR173657 treatment restored it significantly to 100%. These results suggest that the endogenous kinins generated from the kallikrein-kinin system have a significant role in the development of EC. Topics: Animals; Bradykinin Receptor Antagonists; Colitis; Colon; Dextran Sulfate; Kininogens; Kinins; Male; Quinolines; Rats; Rats, Inbred BN; Rats, Mutant Strains; Rats, Sprague-Dawley; Receptor, Bradykinin B2; Receptors, Bradykinin | 2002 |