Document Detail

Role of the intestinal bile acid transporters in bile acid and drug disposition.
MedLine Citation:
PMID:  21103970     Owner:  NLM     Status:  MEDLINE    
Membrane transporters expressed by the hepatocyte and enterocyte play critical roles in maintaining the enterohepatic circulation of bile acids, an effective recycling and conservation mechanism that largely restricts these potentially cytotoxic detergents to the intestinal and hepatobiliary compartments. In doing so, the hepatic and enterocyte transport systems ensure a continuous supply of bile acids to be used repeatedly during the digestion of multiple meals throughout the day. Absorption of bile acids from the intestinal lumen and export into the portal circulation is mediated by a series of transporters expressed on the enterocyte apical and basolateral membranes. The ileal apical sodium-dependent bile acid cotransporter (abbreviated ASBT; gene symbol, SLC10A2) is responsible for the initial uptake of bile acids across the enterocyte brush border membrane. The bile acids are then efficiently shuttled across the cell and exported across the basolateral membrane by the heteromeric Organic Solute Transporter, OSTα-OSTβ. This chapter briefly reviews the tissue expression, physiology, genetics, pathophysiology, and transport properties of the ASBT and OSTα-OSTβ. In addition, the chapter discusses the relationship between the intestinal bile acid transporters and drug metabolism, including development of ASBT inhibitors as novel hypocholesterolemic or hepatoprotective agents, prodrug targeting of the ASBT to increase oral bioavailability, and involvement of the intestinal bile acid transporters in drug absorption and drug-drug interactions.
Paul A Dawson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Handbook of experimental pharmacology     Volume:  -     ISSN:  0171-2004     ISO Abbreviation:  Handb Exp Pharmacol     Publication Date:  2011  
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-02-25     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  7902231     Medline TA:  Handb Exp Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  169-203     Citation Subset:  IM    
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MeSH Terms
Bile Acids and Salts / metabolism*
Biological Transport
Drug Interactions
Enterohepatic Circulation
Intestinal Absorption
Intestines / drug effects,  metabolism*
Membrane Transport Proteins / chemistry,  drug effects,  genetics,  metabolism*
Organic Anion Transporters, Sodium-Dependent / antagonists & inhibitors,  metabolism
Pharmaceutical Preparations / metabolism*
Protein Conformation
Structure-Activity Relationship
Symporters / antagonists & inhibitors,  metabolism
Grant Support
Reg. No./Substance:
0/Bile Acids and Salts; 0/Membrane Transport Proteins; 0/Organic Anion Transporters, Sodium-Dependent; 0/Pharmaceutical Preparations; 0/Symporters; 0/organic solute transporter alpha, human; 0/organic solute transporter beta, human; 145420-23-1/sodium-bile acid cotransporter

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