Document Detail


The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) in physiology and pathophysiology of bile formation.
MedLine Citation:
PMID:  21103971     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bile formation is an important function of the liver. Bile salts are a major constituent of bile and are secreted by hepatocytes into bile and delivered into the small intestine, where they assist in fat digestion. In the small intestine, bile salts are almost quantitatively reclaimed and transported back via the portal circulation to the liver. In the liver, hepatocytes take up bile salts and secrete them again into bile for ongoing enterohepatic circulation. Uptake of bile salts into hepatocytes occurs largely in a sodium-dependent manner by the sodium taurocholate cotransporting polypeptide NTCP. The transport properties of NTCP have been extensively characterized. It is an electrogenic member of the solute carrier family of transporters (SLC10A1) and transports predominantly bile salts and sulfated compounds, but is also able to mediate transport of additional substrates, such as thyroid hormones, drugs and toxins. It is highly regulated under physiologic and pathophysiologic conditions. Regulation of NTCP copes with changes of bile salt load to hepatocytes and prevents entry of cytotoxic bile salts during liver disease. Canalicular export of bile salts is mediated by the ATP-binding cassette transporter bile salt export pump BSEP (ABCB11). BSEP constitutes the rate limiting step of hepatocellular bile salt transport and drives enterohepatic circulation of bile salts. It is extensively regulated to keep intracellular bile salt levels low under normal and pathophysiologic situations. Mutations in the BSEP gene lead to severe progressive familial intrahepatic cholestasis. The substrates of BSEP are practically restricted to bile salts and their metabolites. It is, however, subject to inhibition by endogenous metabolites or by drugs. A sustained inhibition will lead to acquired cholestasis, which can end in liver injury.
Authors:
Bruno Stieger
Publication Detail:
Type:  Journal Article; 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:  2011-04-12    
Medline Journal Info:
Nlm Unique ID:  7902231     Medline TA:  Handb Exp Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  205-59     Citation Subset:  IM    
Affiliation:
Division of Clinical Pharmacology and Toxicology, University Hospital, 8091, Zurich, Switzerland. bstieger@kpt.uzh.ch
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / antagonists & inhibitors,  genetics,  metabolism*
Animals
Bile Acids and Salts / metabolism*
Biological Transport
Cholestasis, Intrahepatic / metabolism,  physiopathology
Enterohepatic Circulation
Genotype
Humans
Liver / drug effects,  metabolism*,  physiopathology
Mutation
Organic Anion Transporters, Sodium-Dependent / antagonists & inhibitors,  genetics,  metabolism*
Pharmacogenetics
Phenotype
Phylogeny
Symporters / antagonists & inhibitors,  genetics,  metabolism*
Chemical
Reg. No./Substance:
0/ABCB11 protein, human; 0/ATP-Binding Cassette Transporters; 0/Bile Acids and Salts; 0/Organic Anion Transporters, Sodium-Dependent; 0/Symporters; 145420-23-1/sodium-bile acid cotransporter

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


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