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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-39892

Stieger, B (2011). The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation. Handbook of Experimental Pharmacology, (201):205-259.

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Abstract

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.

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:24 Jan 2011 15:51
Last Modified:27 Nov 2013 18:44
Publisher:Springer
ISSN:0171-2004
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:10.1007/978-3-642-14541-4_5
PubMed ID:21103971
Citations:Web of Science®. Times Cited: 43
Google Scholar™
Scopus®. Citation Count: 48

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