Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to investigate the effects of endothelin(A) receptor antagonist (ET(A)-RA) BQ485; ET(B)-RA BQ788, and nonselective ET(A/B)-RA Bosentan on the gastrointestinal transit of guinea pigs. We further analyzed the distribution of ET-R subtypes on smooth muscle cells (SMC) of the gastrointestinal tract to investigate their direct involvement on SMC in gastrointestinal tract transit. A guinea pig model was used to measure intestinal transit. The effects of Bosentan (100 mg/kg, per os), BQ485 (1 mg/kg, intraperitoneally) and BQ788 (1 mg/kg, intraperitoneally) on transit in stomach, small intestine, and colon were evaluated. We separated SMC from stomach, small intestine, cecum, and colon by collagenase and analyzed the distribution of ET-R subtypes in each part by binding assay. Gastric transit and colon transit were significantly inhibited by BQ485, BQ788, and Bosentan. Small intestinal transit was not affected by any of these agents. ET(A)-R and ET(B)-R were widely distributed on SMC of stomach, small intestine, cecum, and colon. The ratio of ET(A)-R to ET(B)-R was 1:3 in stomach, small intestine, and cecum, but was 1:10 in colon. The ratio of the total number of ET-R on SMC of stomach, small intestine, cecum, and colon was 1:3:9:1. These results indicate that both ET(A)-R and ET(B)-R are strongly involved in the transit in the stomach and colon. However, the discrepancy between the effects of the various ET-R antagonists on gastrointestinal transit and the distribution of ET-R on SMC of the gastrointestinal tract suggests that ET-R on SMC of the gastrointestinal tract is not directly involved in gastrointestinal transit.
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PMID:Effects of several endothelin receptor antagonists on gastrointestinal transit of guinea pigs. 1079 61

Recent data demonstrate the fundamental role of endothelin in the pathogenesis of fibrosis, and the anti-fibrotic potential of dual endothelin receptor antagonists such as bosentan. Although transforming growth factor-beta, aldosterone and connective tissue growth factor, have already been established as contributors to the process of fibrosis, endothelin now emerges as a key player, which may have a role both in the initiation and in maintenance of fibrosis, and may mediate the pro-fibrotic effects of the other agents. Bosentan is an orally active, dual endothelin receptor antagonist, which competitively antagonizes the binding of endothelin to both endothelin receptors ETA and ETB. Bosentan prevents endothelin-induced fibroblast proliferation and extracellular matrix deposition and contraction, and reduces cardiac, hepatic, pulmonary and renal fibrosis in different disease models characterized by the activation of the endothelin system. Bosentan even reverses existing fibrosis, possibly by its effect of stimulating matrix metalloproteinase type 1 (collagenase) expression. The anti-fibrotic effects of bosentan extend to fibrosis induced by mediators other than endothelin such as transforming growth factor-beta, angiotensin II and aldosterone, indicating a central role of endothelin and endothelin receptors in fibrotic processes.
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PMID:Role of endothelin in fibrosis and anti-fibrotic potential of bosentan. 1590 42