Abstract
Bile formation is a key function of the liver and is driven by active secretion of bile salts and other organic compounds into the biliary tree. Bile salts represent the major organic constituent of bile. They are released with bile into the small intestine, where they are almost quantitatively reabsorbed and transported via the portal circulation back to the liver. In the liver, they are taken up into hepatocytes and secreted into bile. This cycling between the liver and the small intestine is called enterohepatic circulation of bile salts. Bile salts are secreted from hepatocytes into the bile by the bile salt export pump BSEP. This step constitutes the rate-limiting step of handling of bile salts in the liver and is the major driving force of the enterohepatic circulation of bile salts. Improper functioning of BSEP leads to an accumulation of bile salts within hepatocytes, where bile salts become cytotoxic. If persistent, accumulation of bile salts in hepatocytes will lead to liver disease. This review summarizes the essential concepts of bile formation and the current knowledge of mechanisms known to impair BSEP function. Finally, it sets the current therapeutic approaches for cholestatic liver disease into perspective to the pathophysiologic mechanisms of impaired BSEP function.
Keywords: ABC transporter, bile formation, BSEP, cholestasis, drug, liver injury, drug-drug interactions, ABCB11, cytochrome P450, mutations, UGT
Current Drug Targets
Title: The Canalicular Bile Salt Export Pump BSEP (ABCB11) as a Potential Therapeutic Target
Volume: 12 Issue: 5
Author(s): Bruno Stieger and Ulrich Beuers
Affiliation:
Keywords: ABC transporter, bile formation, BSEP, cholestasis, drug, liver injury, drug-drug interactions, ABCB11, cytochrome P450, mutations, UGT
Abstract: Bile formation is a key function of the liver and is driven by active secretion of bile salts and other organic compounds into the biliary tree. Bile salts represent the major organic constituent of bile. They are released with bile into the small intestine, where they are almost quantitatively reabsorbed and transported via the portal circulation back to the liver. In the liver, they are taken up into hepatocytes and secreted into bile. This cycling between the liver and the small intestine is called enterohepatic circulation of bile salts. Bile salts are secreted from hepatocytes into the bile by the bile salt export pump BSEP. This step constitutes the rate-limiting step of handling of bile salts in the liver and is the major driving force of the enterohepatic circulation of bile salts. Improper functioning of BSEP leads to an accumulation of bile salts within hepatocytes, where bile salts become cytotoxic. If persistent, accumulation of bile salts in hepatocytes will lead to liver disease. This review summarizes the essential concepts of bile formation and the current knowledge of mechanisms known to impair BSEP function. Finally, it sets the current therapeutic approaches for cholestatic liver disease into perspective to the pathophysiologic mechanisms of impaired BSEP function.
Export Options
About this article
Cite this article as:
Stieger Bruno and Beuers Ulrich, The Canalicular Bile Salt Export Pump BSEP (ABCB11) as a Potential Therapeutic Target, Current Drug Targets 2011; 12 (5) . https://dx.doi.org/10.2174/138945011795378496
DOI https://dx.doi.org/10.2174/138945011795378496 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Autoimmunity and Apoptosis - Therapeutic Implications
Current Medicinal Chemistry Aging in Down Syndrome and the Development of Alzheimer’s Disease Neuropathology
Current Alzheimer Research Update Clinical Application of Diffusion Tensor Imaging
Current Medical Imaging Flavonoids in Human Health: From Structure to Biological Activity
Current Nutrition & Food Science Outpatient Treatment of Hemorrhoidal Disease: The Alternative Way to Treat Hemorrhoidal Disease in a Simple, Safe and Effective Manner
Reviews on Recent Clinical Trials Aetiology, Diagnosis and Treatment of Hydrops Foetalis
Current Pediatric Reviews The Modern Spectrum of Rhabdomyolysis: Drug Toxicity Revealed by Creatine Kinase Screening
Current Drug Safety OMICS-Derived Targets for Inflammatory Gut Disorders: Opportunities for the Development of Nutrition Related Biomarkers
Endocrine, Metabolic & Immune Disorders - Drug Targets Cholestasis During Pregnancy: Aetiopathogenesis, Foetal-Maternal Repercussions and Pharmacological Treatments
Current Women`s Health Reviews Targeting Epigenetics in Nervous System Disease
CNS & Neurological Disorders - Drug Targets Role of Chitosan Biomaterials in Drug Delivery Systems: A Patent Perspective
Recent Patents on Materials Science Development, Characterization and in vivo Localization Study of Topical 5-Fluorouracil Gels: A Comparative Study with Conventional Formulation
Current Drug Delivery The Involvement of Metallothioneins in Mitochondrial Function and Disease
Current Protein & Peptide Science Transgenic Models in Allergic Responses
Current Drug Targets Immunotherapeutic Options for Pediatric Malignancies
Current Immunology Reviews (Discontinued) A Review on the Use of Statins and Tocotrienols, Individually or in Combination for the Treatment of Osteoporosis
Current Drug Targets Possible Therapeutic Targets in Cardiac Myocyte Apoptosis
Current Pharmaceutical Design Nanoparticle Interaction with Biomolecules: How it Shapes the Nano-Effects on Immunity
Current Bionanotechnology (Discontinued) Regulation of p53 Activity
Current Chemical Biology Free ISG15 and Protein ISGylation Emerging in SARS-CoV-2 Infection
Current Drug Targets