The DOI matches its Crossref record; 123 of the 123 references it cites were found in a registry or an index.
Molecular aspects of hepatobiliary transport
Abstract
Generation of bile flow is a regulated, ATP-dependent process and depends on the coordinated action of a number of transporter proteins in the sinusoidal and canalicular domains of the hepatocyte. Dysfunction of any of these proteins leads to retention of substrates, with conjugated hyperbilirubinemia or cholestasis as a result. In recent years many of the transport proteins involved in bile formation have been identified, cloned, and functionally characterized. The hepatocyte sinusoidal membrane contains transport proteins for the hepatic uptake of organic anions and cations and for the uptake of bile acids. The multispecific organic anion transporting polypeptide (OATP) mediates the hepatic uptake of organic anions and a variety of organic amphiphilic compounds, including organic cations. The organic cation transporter OCT1 more specifically transports small organic cations. NTCP is the Na(+)-bile acid cotransporting protein that mediates the hepatic uptake of bile acids. The canalicular transport proteins are able to transport endogenous and exogenous metabolites into the bile against steep concentration gradients. Most of these transporters are members of the large ATP-binding cassette (ABC) superfamily, and their transport function directly depends on the hydrolysis of Mg2+/ATP. At least five ABC transporter proteins have been characterized so far: 1) the human multidrug resistance protein MDR1 mediates the excretion of hydrophobic, mostly cationic, metabolites; 2) MDR3 is involved in phosphatidylcholine secretion; 3) the canalicular bile acid transporter cBAT mediates secretion of monovalent bile salts and provides the molecular basis of bile acid-dependent bile flow; 4) SPGP, product of the P-glycoprotein sister gene, is exclusively expressed in the liver but its function is currently unknown; and 5) the human multidrug resistance protein MRP2 mediates the excretion of multivalent anionic conjugates.
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Cited by
Bile salt transporters: molecular characterization, function, and regulation
Trauner, M., & Boyer, J. L. (2003) · Physiological Reviews · doi:10.1152/physrev.00027.2002 · Cited by 999
To Scale or Not to Scale: The Principles of Dose Extrapolation
Sharma, V., & McNeill, J. H. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00267.x · Cited by 544
Cha, S. H., Sekine, T., Fukushima, J.-I., Kanai, Y., Kobayashi, Y., Goya, T., & Endou, H. (2001) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)12589-8 · Cited by 508
Impact of Drug Transporter Studies on Drug Discovery and Development
Mizuno, N., Niwa, T., Yotsumoto, Y., & Sugiyama, Y. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.3.1 · Cited by 490
EVALUATION OF DRUG-DRUG INTERACTION IN THE HEPATOBILIARY AND RENAL TRANSPORT OF DRUGS
Shitara, Y., Sato, H., & Sugiyama, Y. (2005) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.44.101802.121444 · Cited by 336
Metadata
- Authors
- Muller, M., & Jansen, P. L.
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 1997-06-01
- Volume
- 272
- Issue
- 6
- Pages
- G1285-G1303
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2143808974
- Cited by
- 299
- References
- 123
- FWCI
- 13.60
- Type
- journal article
- Language
- en
- Open access
- closed
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