Document Detail

Ursodeoxycholic acid action on the transport function of the small intestine in normal and cystic fibrosis mice.
MedLine Citation:
PMID:  11732748     Owner:  NLM     Status:  MEDLINE    
Ursodeoxycholic acid possesses choleretic and cytoprotective properties and in cystic fibrosis (CF) it is used to treat the hepatobiliary symptoms of the disease. This study investigated the effects of this bile acid on the transport function of the small intestine in normal and CF mice. The effects of ursodeoxycholic acid were monitored as changes in short-circuit current (SCC) in stripped sheets of small intestine from normal (Swiss MF1) and transgenic CF (Cftr(tm2Cam)) mice. In ileal sheets from Swiss MF1 mice, mucosal ursodeoxycholic acid caused a biphasic increase in SCC. The first phase was reduced by lowering the mucosal Na+ concentration, while the second phase was inhibited by (Cl-)-free conditions, serosal furosemide or mucosal diphenylamine-2-carboxylic acid (DPC), suggesting an initial Na+-dependent bile acid absorption followed by a stimulation of electrogenic Cl- secretion. Serosal application of ursodeoxycholic acid to the ileum and mucosal or serosal application to the mid-intestine and jejunum elicited a secretory response only. Secretion was Ca2+-dependent, but did not involve neural mechanisms. Mucosal mast cells, histamine and serotonin (5-HT) were implicated in the secretory response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 mice, but the secretory response to mucosal or serosal application of the bile acid was impaired in CF tissues. In ilea from CF mice the initial absorptive phase of the response to mucosal ursodeoxycholic acid was still observed. It is concluded that ursodeoxycholic acid induces secretion throughout the murine small intestine by a mechanism that involves degranulation of mucosal mast cells. In the ileum Na+-dependent absorption can also be detected. The secretory response is defective in CF intestine, but the absorptive effect is still present.
J Hardcastle; P T Hardcastle; J Chapman; C J Taylor
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  53     ISSN:  0022-3573     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-12-04     Completed Date:  2002-04-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1457-67     Citation Subset:  IM    
Department of Biomedical Science, University of Sheffield, UK.
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MeSH Terms
Bile Acids and Salts / pharmacology
Biological Transport / drug effects
Calcium / metabolism
Cholagogues and Choleretics / pharmacology*,  therapeutic use
Cystic Fibrosis / drug therapy*,  metabolism
Dose-Response Relationship, Drug
Intestinal Mucosa / drug effects,  secretion
Intestine, Small / drug effects*,  secretion
Mast Cells / drug effects
Membrane Potentials / drug effects
Mice, Inbred Strains
Mice, Transgenic
Ursodeoxycholic Acid / pharmacology*,  therapeutic use
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholagogues and Choleretics; 128-13-2/Ursodeoxycholic Acid; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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