| Role of the intestinal bile acid transporters in bile acid and drug disposition. | |
| | |
MedLine Citation:
|
PMID: 21103970 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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: 2012-01-04 |
Medline Journal Info:
|
Nlm Unique ID: 7902231 Medline TA: Handb Exp Pharmacol Country: Germany |
Other Details:
|
Languages: eng Pagination: 169-203 Citation Subset: IM |
Affiliation:
|
Department of Internal Medicine, Section on Gastroenterology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA. pdawson@wfubmc.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Bile Acids and Salts / metabolism* Biological Transport Drug Interactions Enterohepatic Circulation Genotype Humans 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* Phenotype Protein Conformation Structure-Activity Relationship Symporters / antagonists & inhibitors, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
DK047987/DK/NIDDK NIH HHS; R01 DK047987-17/DK/NIDDK NIH HHS |
| Chemical | |
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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Organic cation transporters (OCTs, MATEs), in vitro and in vivo evidence for the importance in drug ...
Next Document: The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pu...