The Bile Salt Export Pump

Department of Medicine, Institute of Clinical Pharmacology and Toxicology, University Hospital, Zürich, Switzerland.
Pflügers Archiv - European Journal of Physiology (Impact Factor: 4.1). 03/2007; 453(5):611-20. DOI: 10.1007/s00424-006-0152-8
Source: PubMed


Canalicular secretion of bile salts mediated by the bile salt export pump Bsep constitutes the major driving force for the generation of bile flow. Bsep is a member of the B-family of the super family of ATP-binding cassette transporters and is classified as ABCB11. Bsep has a narrow substrate specificity, which is largely restricted to bile salts. Bsep is extensively regulated at the transcriptional and posttranscriptional level, which directly modulates canalicular bile formation. Pathophysiological alterations of Bsep by either inherited mutations or acquired processes such as inhibition by drugs or disease-related down regulation may lead to a wide spectrum of mild to severe forms of liver disease. Furthermore, many genetic variants of Bsep are known, some of which potentially render individuals susceptible to acquired forms of liver disease.

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    • "Intra-hepatic cholestasis represents a frequent manifestation of DILI in humans (Lee, 2003). In many cases, it results from alterations of the hepatobiliary transporter system, in particular the bile salt export pump (BSEP), which is the most physiologically important canalicular bile transporter (Stieger et al., 2007). Other disturbances, such as altered cell polarity, disruption of cell-to-cell junctions and cytoskeleton disorganization, can also participate in cholestasis. "
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    • "Later studies revealed additional ABCB transporters as MDR proteins. Besides xenobiotic extrusion (ABCB1, 5, 8) [72]–[74], ABCB members are also known in human biology for the translocation, for example, of phosphatidylcholine (ABCB4) [75], bile acids (ABCB11) [76], peptides (TAP1:TAP2 (antigen processing in the adaptive immune system), TAPL, mitochondrial ABCB10) [77], metabolites of the heme synthetic pathway (ABCB6) [78], or iron (mitochondrial ABCB7 and 8) [79]–[82]. In insects, several examples suggest the involvement of P-glycoproteins in the resistance to insecticides used for crop protection [23], [24], [83]–[91]. "
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    • "For male adults to excrete pheromones, transporters need to provide mechanisms for the bile salts to exit hepatocytes as well as to enter and to exit gill epithelial cells. Expression of bsep, which encodes for an ATP-dependent bile salt export pump (BSEP) that is known for secretions of bile salts out of the hepatocytes [25], remained substantially high in the liver of both maturation states. As expected, the bsep mRNA level specifically increased in the lamprey liver from IM to SM, corresponding with the up-regulation of bile salt synthesis seen in SMs. "
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