Download PDF
Semin Liver Dis 2000; Volume 20(Number 03): 273-292
DOI: 10.1055/s-2000-9426
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Hepatic Transport of Bile Salts

GERD. A. KULLAK-UBLICK, BRUNO. STIEGER, BRUNO. HAGENBUCH, PETER. J. MEIER
  • From the Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, Zürich, Switzerland
Further Information

Publication History

Publication Date:
31 December 2000 (online)

    Permissions and Reprints

ABSTRACT

The vectorial secretion of bile salts from blood into bile is a major driving force for bile formation. The basolateral hepatocyte membrane extracts bile salts from sinusoidal blood via Na+-dependent and Na+-independent membrane transporters. Na+-dependent uptake of bile salts is mediated by the Na+-taurocholate cotransporting polypeptide, a 51-kDa protein that is exclusively expressed in hepatocytes. Na+-independent uptake of bile salts is mediated by the organic anion transporting polypeptides, a superfamily of multispecific bile salt and amphipathic substrate transporters. Within the hepatocyte, bile salts are bound to cytosolic proteins and traverse the cell mainly by diffusion. Transport across the canalicular membrane is the rate-limiting step in overall hepatocellular bile salt excretion and is mediated by the bile salt export pump (BSEP), a homologue of the P-glycoproteins or multidrug resistance gene products. BSEP is a vulnerable target for inhibition by estrogen metabolites, drugs such as cyclosporine A, and abnormal bile salt metabolites, all of which can cause retention of bile salts and consequently intrahepatic cholestasis. Canalicular efflux of divalent sulfated or glucuronidated bile salts is mediated by the multidrug resistance protein 2 (MRP2), which is strongly decreased in cholestasis. Decreased MRP2 expression leads to compensatory increases in the basolateral expression of MRP1 and MRP3, which mediate the sinusoidal efflux of divalent bile salt conjugates and other organic anions. Thus, the hepatocyte can regulate expression levels of individual bile salt transporters during cholestasis to evade hepatotoxic injury.

KEYWORD

organic anions - bile acid transport - cholestasis

REFERENCES

  • 1 Reichen J. The role of the sinusoidal endothelium in liver function.  News Physiol Sci . 1999;  14 117-121
    PubMedGoogle Scholar
  • 2 Hofmann A F. Bile acids: the good, the bad, and the ugly.  News Physiol Sci . 1999;  14 24-29
    PubMedGoogle Scholar
  • 3 Makishima M, Okamoto A Y, Repa J J. Identification of a nuclear receptor for bile acids.  Science . 1999;  284 1362-1365
    CrossrefPubMedGoogle Scholar
  • 4 Meier P J. Molecular mechanisms of hepatic bile salt transport from sinusoidal blood into bile.  Am J Physiol . 1995;  269 G801-G812
    PubMedGoogle Scholar
  • 5 Hofmann A F. Bile secretion and the enterohepatic circulation of bile acids. In: Feldman M, Scharschmidt BF, Sleisenger MH (eds). Gastrointestinal and liver disease Philadelphia: London, W.B. Saunders, 1998: 937-948
    Google Scholar
  • 6 Groothuis G M, Hardonk M J, Keulemans K P. Autoradiographic and kinetic demonstration of acinar heterogeneity of taurocholate transport.  Am J Physiol . 1982;  243 G455-462
    PubMedGoogle Scholar
  • 7 Nathanson M H, Boyer J L. Mechanisms and regulation of bile secretion.  Hepatology . 1991;  14 551-566
    CrossrefPubMedGoogle Scholar
  • 8 Müller M, Jansen P L. Molecular aspects of hepatobiliary transport.  Am J Physiol . 1997;  272 G1285-G1303
    PubMedGoogle Scholar
  • 9 Müller M, Jansen P LM. The secretory function of the liver: new aspects of hepatobiliary transport.  J Hepatol . 1998;  28 344-354
    CrossrefPubMedGoogle Scholar
  • 10 Anwer M S, Hegner D. Effect of Na+ on bile acid uptake by isolated rat hepatocytes: evidence for a heterogeneous system.  Hoppe-Seyler's Z Physiol Chem . 1978;  359 181-192
    PubMedGoogle Scholar
  • 11 Scharschmidt B F, Stephens J E. Transport of sodium, chloride and taurocholate by cultured rat hepatocytes.  Proc Natl Acad Sci USA . 1981;  78 986-990
    PubMedGoogle Scholar
  • 12 Yamazaki M, Suzuki H, Hanano M. Different relationships between cellular ATP and hepatic uptake among taurocholate, cholate, and organic anions.  Am J Physiol . 1993;  264 G693-701
    PubMedGoogle Scholar
  • 13 Boelsterli U A, Zimmerli B, Meier P J. Identification and characterization of a basolateral dicarboxylate-cholate antiport system in rat hepatocytes.  Am J Physiol . 1995;  268 G797-G805
    PubMedGoogle Scholar
  • 14 Kouzuki H, Suzuki H, Ito K. Contribution of sodium taurocholate co-transporting polypeptide to the uptake of its possible substrates into rat hepatocytes.  J Pharmacol Exp Ther . 1998;  286 1043-1050
    PubMedGoogle Scholar
  • 15 Caflisch C, Zimmerli B, Reichen J. Cholate uptake in basolateral rat liver plasma membrane vesicles and in liposomes.  Biochim Biophys Acta . 1990;  1021 70-76
    PubMedGoogle Scholar
  • 16 Reichen J, Paumgartner G. Uptake of bile acids by perfused rat liver.  Am J Physiol . 1976;  231 734-742
    PubMedGoogle Scholar
  • 17 Hofmann A F. Bile acids. In: Arias IM, Boyer JL, Fausto N, et al. (eds) The liver, biology and pathobiology. New York: Raven, 1994: 677-718
    Google Scholar
  • 18 Petzinger E. Transport of organic anions in the liver.  An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport. Rev Physiol Biochem Pharmacol . 1994;  123 47-211
    PubMedGoogle Scholar
  • 19 Suchy F J. Hepatocellular transport of bile acids.  Semin Liv Dis . 1993;  13 235-247
    PubMedGoogle Scholar
  • 20 Bear C E, Davidson J S, Shaffer E A. Sodium-dependent taurocholate uptake by isolated rat hepatocytes occurs through an electrogenic mechanism.  Biochim Biophys Acta . 1987;  903 388-394
    PubMedGoogle Scholar
  • 21 Weinman S A, Graf J, Veith C. Electroneutral uptake and electrogenic secretion of a fluorescent bile salt by rat hepatocyte couplets.  Am J Physiol . 1993;  264 G220-G230
    PubMedGoogle Scholar
  • 22 Hagenbuch B, Stieger B, Foguet M. Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system.  Proc Natl Acad Sci USA . 1991;  88 10629-10633
    PubMedGoogle Scholar
  • 23 Hagenbuch B, Meier P J. Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter.  J Clin Invest . 1994;  93 1326-1331
    CrossrefPubMedGoogle Scholar
  • 24 Cattori V, Eckhardt U, Hagenbuch B. Molecular cloning and functional characterization of two alternatively spliced Ntcp isoforms from mouse liver.  Biochim Biophys Acta . 1999;  1445 154-159
    PubMedGoogle Scholar
  • 25 Kramer W, Stengelin S, Baringhaus K H. Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters.  J Lipid Res . 1999;  40 1604-1617
    PubMedGoogle Scholar
  • 26 Stieger B, Hagenbuch B, Landmann L. In situ localization of the hepatocytic Na+/taurocholate cotransporting polypeptide in rat liver.  Gastroenterology . 1994;  107 1781-1787
    PubMedGoogle Scholar
  • 27 Ananthanarayanan M, Ng O C, Boyer J L. Characterization of cloned rat liver Na+-bile acid cotransporter using peptide and fusion protein antibodies.  Am J Physiol . 1994;  267 G637-G643
    PubMedGoogle Scholar
  • 28 Wright E M, Hager K M, Turk E. Sodium cotransport proteins.  Curr Opin Cell Biol . 1992;  4 696-702
    CrossrefPubMedGoogle Scholar
  • 29 Boyer J L, Ng O-C, Ananthanarayanan M. Expression and characterization of a functional rat liver Na+ bile acid cotransport system in COS-7 cells.  Am J Physiol . 1994;  266 G382-G387
    PubMedGoogle Scholar
  • 30 Kullak-Ublick G A, Ismair M G, Kubitz R. Stable expression and functional characterization of a Na+-taurocholate cotransporting green fluorescent protein in human hepatoblastoma HepG2 cells.  Cytotechnology . 2000;  33
    PubMedGoogle Scholar
  • 31 Hagenbuch B, Scharschmidt B F, Meier P J. Effect of antisense oligonucleotides on the expression of hepatocellular bile acid and organic anion uptake systems in Xenopus laevis oocytes.  Biochem J . 1996;  316 901-904
    PubMedGoogle Scholar
  • 32 Meier P J, Eckhardt U, Schroeder A. Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver.  Hepatology . 1997;  26 1667-1677
    PubMedGoogle Scholar
  • 33 Gartung C, Ananthanarayanan M, Rahman M A. Down-regulation of expression and function of the rat liver Na+/bile acid cotransporter in extrahepatic cholestasis.  Gastroenterology . 1996;  110 199-209
    PubMedGoogle Scholar
  • 34 Dumont M, Jacquemin E, D'Hont C. Expression of the liver Na+-independent organic anion transporting polypeptide (oatp-1) in rats with bile duct ligation.  J Hepatol . 1997;  27 1051-1056
    CrossrefPubMedGoogle Scholar
  • 35 Green R M, Beier D, Gollan J L. Regulation of hepatocyte bile salt transporters by endotoxin and inflammatory cytokines in rodents.  Gastroenterology . 1996;  111 193-198
    CrossrefPubMedGoogle Scholar
  • 36 Moseley R H, Wang W, Takeda H. Effect of endotoxin on bile acid transport in rat liver: a potential model for sepsis-associated cholestasis.  Am J Physiol . 1996;  271 G137-G146
    PubMedGoogle Scholar
  • 37 Simon F R, Fortune J, Iwahashi M. Ethinyl estradiol cholestasis involves alterations in expression of liver sinusoidal transporters.  Am J Physiol . 1996;  271 G1043-G1052
    PubMedGoogle Scholar
  • 38 Gartung C, Schuele S, Schlosser S F. Expression of the rat liver Na+/taurocholate cotransporter is regulated in vivo by retention of biliary constituents but not their depletion.  Hepatology . 1997;  25 284-290
    PubMedGoogle Scholar
  • 39 Koopen N R, Wolters H, Müller M. Hepatic bile salt flux does not modulate level and activity of the sinusoidal Na+-taurocholate cotransporter (ntcp) in rats.  J Hepatol . 1997;  27 699-706
    CrossrefPubMedGoogle Scholar
  • 40 Ganguly T C, Liu Y, Hyde J F. Prolactin increases hepatic Na+/taurocholate cotransport activity and messenger RNA post partum.  Biochem J . 1994;  303 33-36
    PubMedGoogle Scholar
  • 41 Ganguly T C, O'Brien M L, Karpen S J. Regulation of the rat liver sodium-dependent bile acid cotransporter gene by prolactin.  J Clin Invest . 1997;  99 2906-2914
    PubMedGoogle Scholar
  • 42 Dranoff J A, McClure M, Burgstahler A D. Short-term regulation of bile acid uptake by microfilament-dependent translocation of rat ntcp to the plasma membrane.  Hepatology . 1999;  30 223-229
    CrossrefPubMedGoogle Scholar
  • 43 Grüne S, Engelking L R, Anwer M S. Role of intracellular calcium and protein kinases in the activation of hepatic Na+/taurocholate cotransport by cyclic AMP.  J Biol Chem . 1993;  268 17734-17741
    PubMedGoogle Scholar
  • 44 Mukhopadhayay S, Ananthanarayanan M, Stieger B. cAMP increases liver Na+-taurocholate cotransport by translocating transporter to plasma membranes.  Am J Physiol . 1997;  273 G842-G848
    PubMedGoogle Scholar
  • 45 St. Pierre M V, Dufour J F, Arias I M. Disruption of actin organization by cytochalasin D does not impair biliary secretion of organic anions in the rat.  Hepatology . 1997;  25 970-975
    CrossrefPubMedGoogle Scholar
  • 46 Boyer J L, Soroka C J. Vesicle targeting to the apical domain regulates bile excretory function in isolated rat hepatocyte couplets.  Gastroenterology . 1995;  109 1600-1611
    PubMedGoogle Scholar
  • 47 von Dippe P, Amoui M, Alves C. Na+-dependent bile acid transport by hepatocytes is mediated by a protein similar to microsomal epoxide hydrolase.  Am J Physiol . 1993;  264 G528-G534
    PubMedGoogle Scholar
  • 48 von Dippe P, Amoui M, Stellwagen R H. The functional expression of sodium-dependent bile acid transport in Madin Darby canine kidney cells transfected with the cDNA for microsomal epoxide hydrolase.  J Biol Chem . 1996;  271 18176-18180
    CrossrefPubMedGoogle Scholar
  • 49 Zhu Q, von Dippe P, Xing W. Membrane topology and cell surface targeting of microsomal epoxide hydrolase. Evidence for multiple topological orientations.  J Biol Chem . 1999;  274 27898-27904
    CrossrefPubMedGoogle Scholar
  • 50 Alves C, von Dippe P, Amoui M. Bile acid transport into hepatocyte smooth endoplasmic reticulum vesicles is mediated by microsomal epoxide hydrolase, a membrane protein exhibiting two distinct topological orientations.  J Biol Chem . 1993;  268 20148-20155
    PubMedGoogle Scholar
  • 51 Honscha W, Platte H-D, Oesch F. Relationship between the microsomal epoxide hydrolase and the hepatocellular transport of bile acids and xenobiotics.  Biochem J . 1995;  311 975-979
    PubMedGoogle Scholar
  • 52 Forker E L, Luxon B A. Albumin helps mediate removal of taurocholate by rat liver.  J Clin Invest . 1981;  67 1517-1522
    PubMedGoogle Scholar
  • 53 Blitzer B L, Lyons L. Enhancement of Na+-dependent bile acid uptake by albumin: direct demonstration in rat basolateral liver plasma membrane vesicles.  Am J Physiol . 1985;  249 G34-G38
    PubMedGoogle Scholar
  • 54 Zimmerli B, Valantinas J, Meier P J. Multispecificity of Na+-dependent taurocholate uptake in basolateral (sinusoidal) rat liver plasma membrane vesicles.  J Pharmacol Exp Ther . 1989;  250 301-308
    PubMedGoogle Scholar
  • 55 Honscha W, Schulz K, Müller D. Two different mRNAs from rat liver code for the transport of bumetanide and taurocholate in Xenopus laevis oocytes.  Eur J Pharmacol . 1993;  246 227-232
    PubMedGoogle Scholar
  • 56 Frimmer M, Ziegler K. The transport of bile acids in liver cells.  Biochim Biophys Acta . 1988;  947 75-99
    PubMedGoogle Scholar
  • 57 van D yke, Stephens J E, Scharschmidt B F. Bile acid transport in cultured rat hepatocytes.  Am J Physiol . 1982;  243 G484-G492
    PubMedGoogle Scholar
  • 58 Hagenbuch B, Jacquemin E, Meier P J. Na+-dependent and Na+-independent bile acid uptake systems in the liver.  Cell Physiol Biochem . 1994;  4 198-205
    PubMedGoogle Scholar
  • 59 Miyata M, Kudo G, Lee Y H. Targeted disruption of the microsomal epoxide hydrolase gene. Microsomal epoxide hydrolase is required for the carcinogenic activity of 7,12-dimethylbenz[a]anthracene.  J Biol Chem . 1999;  274 23963-23968
    CrossrefPubMedGoogle Scholar
  • 60 Hugentobler G, Meier P J. Multispecific anion exchange in basolateral (sinusoidal) rat liver plasma membrane vesicles.  Am J Physiol . 1986;  251 G656-G664
    PubMedGoogle Scholar
  • 61 Zimmerli B, O'Neill B, Meier P J. Identification of sodium-dependent and sodium-independent dicarboxylate transport systems in rat liver basolateral membrane vesicles.  Pfluegers Arch . 1992;  421 329-335
    CrossrefPubMedGoogle Scholar
  • 62 Blitzer B L, Terzakis C, Scott K A. Hydroxyl-bile acid exchange: a new mechanism for the uphill transport of cholate by basolateral liver plasma membrane vesicles.  J Biol Chem . 1986;  261 12042-12046
    PubMedGoogle Scholar
  • 63 Veith C M, Thalhammer T, Felberbauer F X. Relationship of hepatic cholate transport to regulation of intracellular pH and potassium.  Biochim Biophys Acta . 1992;  1103 51-61
    PubMedGoogle Scholar
  • 64 Anwer M S, Hegner D. Effect of organic anions on bile acid uptake by isolated rat hepatocytes.  Hoppe-Seyler's Z Physiol Chem . 1978;  359 1027-1030
    PubMedGoogle Scholar
  • 65 Elsner R H, Ziegler K. Radiation inactivation of multispecific transport systems for bile acids and xenobiotics in basolateral rat liver plasma membrane vesicles.  J Biol Chem . 1992;  267 9788-9793
    PubMedGoogle Scholar
  • 66 Wehner F, Rosin-Steiner S, Beetz G. The anion transport inhibitor DIDS increases rat hepatocyte K+ conductance via uptake through the bilirubin pathway.  J Physiol Lond . 1993;  471 617-635
    PubMedGoogle Scholar
  • 67 Ishii K, Wolkoff A W. Inhibition of rat hepatocyte organic anion transport by bile acids.  Am J Physiol . 1994;  267 G458-G464
    PubMedGoogle Scholar
  • 68 Eaton D L, Klaassen C D. Carrier-mediated transport of ouabain in isolated hepatocytes.  J Pharmacol Exp Ther . 1978;  205 480-488
    PubMedGoogle Scholar
  • 69 Okudaira K, Yamazaki M, Sawada Y. Correlation between the inhibitory effects of basic drugs on the uptake of cardiac glycosides and taurocholate by isolated rat hepatocytes.  Pharm Res . 1992;  9 1152-1156
    CrossrefPubMedGoogle Scholar
  • 70 Steen H, Merema M, Meijer D KF. A multispecific uptake system for taurocholate, cardiac glycosides and cationic drugs in the liver.  Biochem Pharmacol . 1992;  44 2323-2331
    CrossrefPubMedGoogle Scholar
  • 71 Ziegler K, Lins W, Frimmer M. Hepatocellular transport of cyclosomatostatins: evidence for a carrier system related to the multispecific bile acid transporter.  Biochim Biophys Acta . 1991;  1061 287-296
    PubMedGoogle Scholar
  • 72 Ziegler K, Stuenkel W. Tissue-selective action of pravastatin due to hepatocellular uptake via a sodium-independent bile acid transporter.  Biochim Biophys Acta . 1992;  1139 203-209
    PubMedGoogle Scholar
  • 73 Reichen J, Berk P D. Isolation of an organic anion binding protein from rat liver plasma membrane fractions by affinity chromatography.  Biochem Biophys Res Commun . 1979;  91 484-489
    CrossrefPubMedGoogle Scholar
  • 74 Stremmel W, Gerber M A, Glezerov V. Physicochemical and immunohistological studies of a sulfobromophthalein- and bilirubin-binding protein from rat liver plasma membranes.  J Clin Invest . 1983;  71 1796-1805
    PubMedGoogle Scholar
  • 75 Wolkoff A W, Chung C T. Identification, purification, and partial characterization of an organic anion binding protein from rat liver cell plasma membrane.  J Clin Invest . 1980;  65 1152-1161
    PubMedGoogle Scholar
  • 76 Wolkoff A W, Sosiak A, Greenblatt H C. Immunological studies of an organic anion-binding protein isolated from rat liver cell plasma membrane.  J Clin Invest . 1985;  76 454-459
    PubMedGoogle Scholar
  • 77 Goeser T, Nakata R, Braly L F. The rat hepatocyte plasma membrane organic anion binding protein is immunologically related to the mitochondrial F1 adenosine triphosphate β-subunit.  J Clin Invest . 1990;  86 220-227
    PubMedGoogle Scholar
  • 78 Tiribelli C, Lunazzi G, Luciani M. Isolation of a sulfobromophthalein-binding protein from hepatocyte plasma membrane.  Biochim Biophys Acta . 1978;  532 105-112
    PubMedGoogle Scholar
  • 79 Battiston L, Macagno A, Passamonti S. Specific sequence-directed anti-bilitranslocase antibodies as a tool to detect potentially bilirubin-binding proteins in different tissues of the rat.  FEBS Lett . 1999;  453 351-355
    CrossrefPubMedGoogle Scholar
  • 80 Berk P D, Bradbury M, Zhou S-L. Characterization of membrane transport processes: lessons from the study of BSP, bilirubin, and fatty acid uptake.  Semin Liver Dis . 1996;  16 107-120
    PubMedGoogle Scholar
  • 81 Jacquemin E, Hagenbuch B, Stieger B. Expression cloning of a rat liver Na+-independent organic anion transporter.  Proc Natl Acad Sci USA . 1994;  91 133-137
    PubMedGoogle Scholar
  • 82 Kullak-Ublick G A, Hagenbuch B, Stieger B. Functional characterization of the basolateral rat liver organic anion transporting polypeptide.  Hepatology . 1994;  20 411-416
    CrossrefPubMedGoogle Scholar
  • 83 Satlin L M, Amin V, Wolkoff A W. Organic anion transporting polypeptide mediates organic anion/HCO3 exchange.  J Biol Chem . 1997;  272 26340-26345
    CrossrefPubMedGoogle Scholar
  • 84 Eckhardt U, Schroeder A, Stieger B. Polyspecific substrate uptake by the hepatic organic anion transporter Oatp1 in stably transfected CHO cells.  Am J Physiol . 1999;  276 G1037-G1042
    PubMedGoogle Scholar
  • 85 Hata S, Wang P, Shi X. Transport of dihydroxy bile salts and their taurine conjugates by organic transporting polypeptide 1 (Oatp1) and Na+-taurocholate co-transporting polypeptide (Ntcp) [abstract].  Hepatology . 1999;  30 466A
    PubMedGoogle Scholar
  • 86 Bergwerk A J, Shi X, Ford A C. Immunologic distribution of an organic anion transport protein in rat liver and kidney.  Am J Physiol . 1996;  271 G231-G238
    PubMedGoogle Scholar
  • 87 Reichel C, Gao B, van Montfoort J. Localization and function of the organic anion-transporting polypeptide Oatp2 in rat liver.  Gastroenterology . 1999;  117 688-695
    PubMedGoogle Scholar
  • 88 Angeletti R H, Novikoff P M, Juvvadi S R. The choroid plexus epithelium is the site of the organic anion transport protein in the brain.  Proc Natl Acad Sci USA . 1997;  94 283-286
    CrossrefPubMedGoogle Scholar
  • 89 Gao B, Stieger B, Noe B. Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain.  J Histochem Cytochem . 1999;  47 1255-1263
    PubMedGoogle Scholar
  • 90 Bossuyt X, Müller M, Hagenbuch B. Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver.  J Pharmacol Exp Ther . 1996;  276 891-896
    PubMedGoogle Scholar
  • 91 Friesema E C, Docter R, Moerings E P. Identification of thyroid hormone transporters.  Biochem Biophys Res Commun . 1999;  254 497-501
    CrossrefPubMedGoogle Scholar
  • 92 Li L, Lee T K, Meier P J. Identification of glutathione as a driving force and leukotriene C4 as a substrate for Oatp1, the hepatic sinusoidal organic solute transporter.  J Biol Chem . 1998;  273 16184-16191
    CrossrefPubMedGoogle Scholar
  • 93 Kanai N, Lu R, Bao Y. Transient expression of oatp organic anion transporter in mammalian cells: identification of candidate substrates.  Am J Physiol . 1996;  270 F319-F325
    PubMedGoogle Scholar
  • 94 Eckhardt U, Horz J A, Petzinger E. The peptide-based thrombin inhibitor CRC 220 is a new substrate of the basolateral rat liver organic anion-transporting polypeptide.  Hepatology . 1996;  24 380-384
    PubMedGoogle Scholar
  • 95 Kontaxi M, Eckhardt U, Hagenbuch B. Uptake of the mycotoxin Ochratoxin A in liver cells occurs via the cloned organic anion transporting polypeptide.  J Pharmacol Exp Ther . 1996;  279 1507-1513
    PubMedGoogle Scholar
  • 96 van Montfoort J E, Stieger B, Meijer D KF. Hepatic uptake of the magnetic resonance imaging contrast agent gadoxetate by the organic anion transporting polypeptide Oatp1.  J Pharmacol Exp Ther . 1999;  290 153-157
    PubMedGoogle Scholar
  • 97 Pang K S, Wang P J, Chung A Y. The modified dipeptide, enalapril, an angiotensin-converting enzyme inhibitor, is transported by the rat liver organic anion transport protein.  Hepatology . 1998;  28 1341-1346
    CrossrefPubMedGoogle Scholar
  • 98 Ishizuka H, Konno K, Naganuma H. Transport of temocaprilat into rat hepatocytes: role of organic anion transporting polypeptide.  J Pharmacol Exp Ther . 1998;  287 37-42
    PubMedGoogle Scholar
  • 99 Hsiang B, Zhu Y, Wang Z. A novel human hepatic organic anion transporting polypeptide (OATP2).  J Biol Chem . 1999;  274 37161-37168
    CrossrefPubMedGoogle Scholar
  • 100 Gao B, Hagenbuch B, Kullak-Ublick G A. Organic anion transporting polypeptides mediate transport of opioid peptides across the blood-brain barrier.  J Pharmacol Exp Ther . 2000;  294 73-79
    Google Scholar
  • 101 Cvetkovic M, Leake B, Fromm M F. OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine.  Drug Metab Dispos . 1999;  27 866-871
    PubMedGoogle Scholar
  • 102 van Montfoort J E, Hagenbuch B, Fattinger K E. Polyspecific organic anion transporting polypeptides mediate hepatic uptake of amphipathic type II organic cations.  J Pharmacol Exp Ther . 1999;  291 147-152
    PubMedGoogle Scholar
  • 103 Hagenbuch B, Adler I-D, Schmid T E. Molecular cloning and functional characterization of the mouse organic-anion-transporting polypeptide 1 (Oatp1) and mapping of the gene to chromosome X.  Biochem J . 2000;  345 115-120
    CrossrefPubMedGoogle Scholar
  • 104 Shi X, Bai S, Ford A C. Stable inducible expression of a functional rat liver organic anion transport protein in HeLa cells.  J Biol Chem . 1995;  270 25591-25595
    CrossrefPubMedGoogle Scholar
  • 105 Glavy J S, Wu S M, Wang P J. Down-regulation by extracellular ATP of rat hepatocyte organic anion transport is mediated by serine phosphorylation of Oatp1.  J Biol Chem . 2000;  275 1479-1484
    CrossrefPubMedGoogle Scholar
  • 106 Noé B, Hagenbuch B, Stieger B. Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain.  Proc Natl Acad Sci USA . 1997;  94 10346-10350
    CrossrefPubMedGoogle Scholar
  • 107 Abe T, Kakyo M, Sakagami H. Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2.  J Biol Chem . 1998;  273 22395-22401
    CrossrefPubMedGoogle Scholar
  • 108 Tokui T, Nakai D, Nakagomi R. Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat organic anion transporting polypeptide, oatp2.  Pharm Res . 1999;  16 904-908
    CrossrefPubMedGoogle Scholar
  • 109 Kakyo M, Sakagami H, Nishio T. Immunohistochemical distribution and functional characterization of an organic anion transporting polypeptide 2 (oatp2).  FEBS Lett . 1999;  445 343-346
    CrossrefPubMedGoogle Scholar
  • 110 Dubuisson C, Cresteil D, Desrochers M. Ontogenic expression of the Na+-independent organic anion transporting polypeptide (oatp) in rat liver and kidney.  J Hepatol . 1996;  25 932-940
    CrossrefPubMedGoogle Scholar
  • 111 Hagenbuch N, Reichel C, Stieger B. Effect of phenobarbital on the expression of hepatocellular bile acid and organic anion transport proteins [abstract].  Hepatology . 1999;  30 466A
    PubMedGoogle Scholar
  • 112 Klaassen C D. Effects of phenobarbital on the plasma disappearance and biliary excretion of drugs in rats.  J Pharmacol Exp Ther . 1970;  175 289-300
    PubMedGoogle Scholar
  • 113 Greenberger N J, Thomas F B. Biliary excretion of 3H-digitoxin: modification by bile salts and phenobarbital.  J Lab Clin Med . 1973;  81 241-251
    PubMedGoogle Scholar
  • 114 Klaassen C D. Effect of microsomal enzyme inducers on the biliary excretion of cardiac glycosides.  J Pharmacol Exp Ther . 1974;  191 201-211
    PubMedGoogle Scholar
  • 115 Thompson T N, Klaassen C D. The effects of hepatic microsomal enzyme inducers on the pharmacokinetics of ouabain after portal and systemic administration to rats.  J Pharm Pharmacol . 1995;  47 1041-1047
    PubMedGoogle Scholar
  • 116 McClain R M, Levin A A, Posch R. The effect of phenobarbital on the metabolism and excretion of thyroxine in rats.  Toxicol Appl Pharmacol . 1989;  99 216-228
    CrossrefPubMedGoogle Scholar
  • 117 Berthelot P, Erlinger S, Dhumeaux D. Mechanism of phenobarbital-induced hypercholeresis in the rat.  Am J Physiol . 1970;  219 809-813
    PubMedGoogle Scholar
  • 118 Li L, Meier P J, Ballatori N. Oatp2 mediates bidirectional organic solute transport: a role for intracellular glutathione.  Mol Pharmacol 2000. in press; 
    PubMedGoogle Scholar
  • 119 Kakyo M, Unno M, Tokui T. Molecular characterization and functional regulation of a novel rat liver-specific organic anion transporter rlst-1.  Gastroenterology . 1999;  117 770-775
    PubMedGoogle Scholar
  • 120 Cattori V, Hagenbuch B, Hagenbuch N. Identification of a novel rat organic anion transporting polypeptide (Oatp4) as a full-length isoform of the liver-specific transporter-1 (rlst-1).  FEBS Lett . 2000;  474 24-245
    PubMedGoogle Scholar
  • 121 Kanai N, Lu R, Satriano J A. Identification and characterization of a prostaglandin transporter.  Science . 1995;  268 866-869
    PubMedGoogle Scholar
  • 122 Saito H, Masuda S, Inui K-I. Cloning and functional characterization of a novel rat organic anion transporter mediating basolateral uptake of methotrexate in the kidney.  J Biol Chem . 1996;  271 20719-20725
    CrossrefPubMedGoogle Scholar
  • 123 Masuda S, Ibaramoto K, Takeuchi A. Cloning and functional characterization of a new multispecific organic anion transporter, OAT-K2, in rat kidney.  Mol Pharmacol . 1999;  55 743-752
    PubMedGoogle Scholar
  • 124 Abe T, Kakyo M, Tokui T. Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1.  J Biol Chem . 1999;  274 17159-17163
    CrossrefPubMedGoogle Scholar
  • 125 König J, Cui Y, Nies A T. A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane.  Am J Physiol . 2000;  278 G156-G164
    PubMedGoogle Scholar
  • 126 Kullak-Ublick G A, Hagenbuch B, Stieger B. Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver.  Gastroenterology . 1995;  109 1274-1282
    PubMedGoogle Scholar
  • 127 Bossuyt X, Müller M, Meier P J. Multispecific amphipathic substrate transport by an organic anion transporter of human liver.  J Hepatol . 1996;  25 733-738
    CrossrefPubMedGoogle Scholar
  • 128 Kullak-Ublick G A, Fisch T, Oswald M. Dehydroepiandrosterone sulfate (DHEAS): identification of a carrier protein in human liver and brain.  FEBS Lett . 1998;  424 173-176
    CrossrefPubMedGoogle Scholar
  • 129 Pascolo L, Cupelli F, Anelli P L. Molecular mechanisms for the hepatic uptake of magnetic resonance imaging contrast agents.  Biochem Biophys Res Commun . 1999;  257 746-752
    CrossrefPubMedGoogle Scholar
  • 130 Kullak-Ublick G A, Glasa J, Boeker C. Chlorambucil-taurocholate is transported by bile acid carriers expressed in human hepatocellular carcinomas.  Gastroenterology . 1997;  113 1295-1305
    PubMedGoogle Scholar
  • 131 Lu R, Kanai N, Bao Y. Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA (hPGT).  J Clin Invest . 1996;  98 1142-1149
    PubMedGoogle Scholar
  • 132 Cotting J, Zysset T, Reichen J. Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake.  Am J Physiol . 1989;  256 G312-G318
    PubMedGoogle Scholar
  • 133 Rahner C, Stieger B, Landmann L. Structure-function correlation of tight junctional impairment after intrahepatic and extrahepatic cholestasis in rat liver.  Gastroenterology . 1996;  110 1564-1578
    PubMedGoogle Scholar
  • 134 Trauner M, Meier P J, Boyer J L. Molecular pathogenesis of cholestasis.  N Engl J Med . 1998;  339 1217-1227
    CrossrefPubMedGoogle Scholar
  • 135 Kullak-Ublick G A, Beuers U, Paumgartner G. Hepatobiliary transport.  J Hepatol . 2000;  3-18 (3-18)
    PubMedGoogle Scholar
  • 136 Kullak-Ublick G A, Meier P J. Mechanisms of cholestasis.  Clin Liver Dis . 2000;  4 357-385
    PubMedGoogle Scholar
  • 137 Trauner M, Arrese M, Soroka C J. The rat canalicular conjugate export pump (mrp2) is down-regulated in intrahepatic and obstructive cholestasis.  Gastroenterology . 1997;  113 255-264
    CrossrefPubMedGoogle Scholar
  • 138 Lee J M, Trauner M, Soroka C J. Expression of the bile salt export pump is maintained after chronic cholestasis in the rat.  Gastroenterology . 2000;  118 163-172
    CrossrefPubMedGoogle Scholar
  • 139 Vos T A, Hooiveld G JEJ, Koning H. Up-regulation of the multidrug resistance genes, mrp1 and mdr1b, and down-regulation of the organic anion transporter, mrp2, and the bile salt transporter, spgp, in endotoxemic rat liver.  Hepatology . 1998;  28 1637-1644
    CrossrefPubMedGoogle Scholar
  • 140 Hirohashi T, Suzuki H, Ito K. Hepatic expression of multidrug resistance-associated protein-like proteins maintained in Eisai hyperbilirubinemic rats.  Mol Pharmacol . 1998;  53 1068-1075
    PubMedGoogle Scholar
  • 141 Stieger B, Meier P J. Bile acid and xenobiotic transporters in liver.  Curr Opin Cell Biol . 1998;  10 462-467
    CrossrefPubMedGoogle Scholar
  • 142 Keppler D, König J, Rost D. ATP-dependent hepatocellular export pumps of the MRP family. In: Paumgartner G, Stiehl A, Gerok W, et al (eds). Bile acids and cholestasis. Dordrecht: Kluwer Academic Publishers, 1999: 106-110
    Google Scholar
  • 143 Frohling W, Stiehl A. Bile salt glucuronides: identification and quantitative analysis in the urine of patients with cholestasis.  Eur J Clin Invest . 1976;  6 67-74
    PubMedGoogle Scholar
  • 144 Stiehl A, Raedsch R, Rudolph G. Biliary and urinary excretion of sulfated, glucuronidated and tetrahydroxylated bile acids in cirrhotic patients.  Hepatology . 1985;  5 492-495
    CrossrefPubMedGoogle Scholar
  • 145 Lund M, Kang L, Tygstrup N. Effects of LPS on transport of indocyanine green and alanine uptake in perfused rat liver.  Am J Physiol . 1999;  277 G91-G100
    PubMedGoogle Scholar
  • 146 Kullak-Ublick G A, Beuers U, Fahney C. Identification and functional characterization of the promoter region of the human organic anion transporting polypeptide gene.  Hepatology . 1997;  26 991-997
    PubMedGoogle Scholar
  • 147 Hirohashi T, Suzuki H, Takikawa H. ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (mrp3).  J Biol Chem . 2000;  275 2905-2910
    CrossrefPubMedGoogle Scholar
  • 148 Crawford J M, Berken C A, Gollan J L. Role of the hepatocyte microtubular system in the excretion of bile salts and biliary lipid: implications for intracellular vesicular transport.  J Lipid Res . 1988;  29 144-156
    PubMedGoogle Scholar
  • 149 Erlinger S. Do intracellular organelles have any role in transport of bile acids by hepatocytes?.  J Hepatol . 1996;  88-93 (88-93)
    PubMedGoogle Scholar
  • 150 Crawford J M, Barnes S, Stearns R C. Ultrastructural localization of a fluorinated bile salt in hepatocytes.  Lab Invest . 1994;  71 42-51
    PubMedGoogle Scholar
  • 151 Stolz A, Takikawa H, Ookhtens M. The role of cytoplasmic proteins in hepatic bile acid transport.  Annu Rev Physiol . 1989;  51 161-176
    CrossrefPubMedGoogle Scholar
  • 152 Takikawa H, Stolz A, Sugiyama Y. Relationship between the newly identified bile acid binder and bile acid oxidoreductases in human liver.  J Biol Chem . 1990;  265 2132-2136
    PubMedGoogle Scholar
  • 153 Stolz A, Rahimi Kiani M, Ameis D. Molecular structure of rat hepatic 3 alpha-hydroxysteroid dehydrogenase. A member of the oxidoreductase gene family.  J Biol Chem . 1991;  266 15253-15257
    PubMedGoogle Scholar
  • 154 Stolz A, Hammond L, Lou H. cDNA cloning and expression of the human hepatic bile acid-binding protein.  J Biol Chem . 1993;  268 10448-10457
    PubMedGoogle Scholar
  • 155 Sugiyama Y, Yamada T, Kaplowitz N. Newly identified bile acid binders in rat liver cytosol: purification and comparison with glutathione S-transferases.  J Biol Chem . 1983;  258 3602-3607
    PubMedGoogle Scholar
  • 156 Dietrich A, Dieminger W, Fuchte K. Functional significance of interaction of H-FABP with sulfated and nonsulfated taurine-conjugated bile salts in rat liver.  J Lipid Res . 1995;  36 1745-1755
    PubMedGoogle Scholar
  • 157 Takikawa H, Stolz A, Sugimoto M. Comparison of the affinities of newly identified human bile acid binder and cationic glutathione S-transferase for bile acids.  J Lipid Res . 1986;  27 652-657
    PubMedGoogle Scholar
  • 158 Crawford J M. Role of vesicle-mediated transport pathways in hepatocellular bile secretion.  Semin Liver Dis . 1996;  16 169-189
    PubMedGoogle Scholar
  • 159 Kast C, Stieger B, Winterhalter K H. Hepatocellular transport of bile acids. Evidence for distinct subcellular localizations of electrogenic and ATP-dependent taurocholate transport in rat hepatocytes.  J Biol Chem . 1994;  269 5179-5186
    PubMedGoogle Scholar
  • 160 Lamri Y, Roda A, Dumont M. Immunoperoxidase localization of bile salts in rat liver cells. Evidence for a role of the Golgi apparatus in bile salt transport.  J Clin Invest . 1988;  82 1173-1182
    PubMedGoogle Scholar
  • 161 Kitamura T, Gatmaitan Z, Arias I M. Serial quantitative image analysis and confocal microscopy of hepatic uptake, intracellular distribution and biliary secretion of a fluorescent bile acid analog in rat hepatocyte doublets.  Hepatology . 1990;  12 1358-1364
    PubMedGoogle Scholar
  • 162 Wilton J C, Matthews G M, Burgoyne R D. Fluorescent choleretic and cholestatic bile salts take different paths across the hepatocyte: transcytosis of glycolithocholate leads to an extensive redistribution of annexin II.  J Cell Biol . 1994;  127 401-410
    CrossrefPubMedGoogle Scholar
  • 163 El Seaidy A Z, Mills C O, Elias E. Lack of evidence for vesicle trafficking of fluorescent bile salts in rat hepatocyte couplets.  Am J Physiol . 1997;  272 G298-G309
    PubMedGoogle Scholar
  • 164 Reynier M O, Abou Hashieh I, Crotte C. Monensin action on the Golgi complex in perfused rat liver: evidence against bile salt vesicular transport.  Gastroenterology . 1992;  102 2024-2032
    PubMedGoogle Scholar
  • 165 Crawford J M, Vinter D W, Gollan J L. Taurocholate induces pericanalicular localization of C6-NBD-ceramide in isolated hepatocyte couplets.  Am J Physiol . 1991;  260 G119-G132
    PubMedGoogle Scholar
  • 166 Cohen D E, Leonard M R, Carey M C. In vitro evidence that phospholipid secretion into bile may be coordinated intracellularly by the combined actions of bile salts and the specific phosphatidylcholine transfer protein of liver.  Biochemistry . 1994;  33 9975-9980
    CrossrefPubMedGoogle Scholar
  • 167 Marks D L, LaRusso N F, McNiven M A. Isolation of the microtubule-vesicle motor kinesin from rat liver: selective inhibition by cholestatic bile acids.  Gastroenterology . 1995;  108 824-833
    PubMedGoogle Scholar
  • 168 Graf J, Häussinger D. Ion transport in hepatocytes: mechanisms and correlations to cell volume, hormone actions and metabolism.  J Hepatol . 1996;  53-77 (53-77)
    PubMedGoogle Scholar
  • 169 Stieger B, Landmann L. Effects of cholestasis on membrane flow and surface polarity in hepatocytes.  J Hepatol . 1996;  128-134 (128-134)
    PubMedGoogle Scholar
  • 170 Häussinger D, Saha N, Hallbrucker C. Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver.  Biochem J . 1993;  291 355-360
    PubMedGoogle Scholar
  • 171 Meier P J. Canalicular membrane transport processes . In: Tavoloni N, Berk PD (eds) Hepatic transport and bile secretion: physiology and pathophysiology. New York: Raven Press, 1993: 587-595
    Google Scholar
  • 172 Meier P J, Meier-Abt A S, Barrett C. Mechanisms of taurocholate transport in canalicular and basolateral rat liver plasma membrane vesicles.  J Biol Chem . 1984;  259 10614-10622
    PubMedGoogle Scholar
  • 173 Nishida T, Gatmaitan Z, Che M. Rat liver canalicular membrane vesicles contain an ATP-dependent bile acid transport system.  Proc Natl Acad Sci USA . 1991;  88 6590-6594
    CrossrefPubMedGoogle Scholar
  • 174 Stieger B, O'Neill B, Meier P J. ATP-dependent bile salt transport in canalicular rat liver plasma-membrane vesicles.  Biochem J . 1992;  284 67-84
    PubMedGoogle Scholar
  • 175 Mills C O, Milkiewicz P, Müller M. Different pathways of canalicular secretion of sulfated and non-sulfated fluorescent bile acids: a study in isolated hepatocyte couplets and TR- rats.  J Hepatol . 1999;  31 678-684
    CrossrefPubMedGoogle Scholar
  • 176 Müller M, Ishikawa T, Berger U. ATP-dependent transport of taurocholate across the hepatocyte canalicular membrane mediated by a 110-kDa glycoprotein binding ATP and bile salt.  J Biol Chem . 1991;  266 18920-18926
    PubMedGoogle Scholar
  • 177 Suchy F J, Sippel C J, Ananthanarayanan M. Bile acid transport across the hepatocyte canalicular membrane.  FASEB J . 1997;  11 199-205
    PubMedGoogle Scholar
  • 178 Sippel C J, Suchy F J, Ananthanarayanan M. The rat liver ecto-ATPase is also a canalicular bile acid transport protein.  J Biol Chem . 1993;  268 2083-2091
    PubMedGoogle Scholar
  • 179 Brown Jr R S, Lomri N, De Voss J. Enhanced secretion of glycocholic acid in a specially adapted cell line is associated with overexpression of apparently novel ATP-binding cassette proteins.  Proc Natl Acad Sci USA . 1995;  92 5421-5425
    PubMedGoogle Scholar
  • 180 Luther T T, Hammerman P, Rahmaoui C M. Evidence for an ATP-dependent bile acid transport protein other than the canalicular liver ecto-ATPase in rats.  Gastroenterology . 1997;  113 249-254
    PubMedGoogle Scholar
  • 181 Ortiz D F, St. Pierre M V, Abdulmessih A. A yeast ATP-binding cassette-type protein mediating ATP-dependent bile acid transport.  J Biol Chem . 1997;  272 15358-15365
    CrossrefPubMedGoogle Scholar
  • 182 Childs S, Lin Yeh R, Georges E. Identification of a sister gene to P-glycoprotein.  Cancer Res . 1995;  55 2029-2034
    PubMedGoogle Scholar
  • 183 Gerloff T, Stieger B, Hagenbuch B. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver.  J Biol Chem . 1998;  273 10046-10050
    CrossrefPubMedGoogle Scholar
  • 184 Strautnieks S S, Bull L N, Knisely A S. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.  Nat Genet . 1998;  20 233-238
    CrossrefPubMedGoogle Scholar
  • 185 Jansen P L, Strautnieks S S, Jacquemin E. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis.  Gastroenterology . 1999;  117 1370-1379
    CrossrefPubMedGoogle Scholar
  • 186 Ballatori N, Rebbeor J F, Connolly G C. Bile salt excretion in skate liver is mediated by a functional analog of Bsep/Spgp, the bile salt export pump.  Am J Physiol . 2000;  278 G57-G63
    PubMedGoogle Scholar
  • 187 Lecureur V, Sun D, Hargrove P. Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein.  Mol Pharmacol . 2000;  57 24-35
    PubMedGoogle Scholar
  • 188 Green R M, Hoda F, Ward K L. Molecular cloning and characterization of the murine bile salt export pump.  Gene . 2000;  241 117-123
    CrossrefPubMedGoogle Scholar
  • 189 Khanuja B, Cheah Y C, Hunt M. Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice.  Proc Natl Acad Sci USA . 1995;  92 7729-7733
    CrossrefPubMedGoogle Scholar
  • 190 Bouchard G, Nelson H M, Lammert F. High-resolution maps of the murine chromosome 2 region containing the cholesterol gallstone locus, Lith1.  Mamm Genome . 1999;  10 1070-1074
    CrossrefPubMedGoogle Scholar
  • 191 Lammert F, Beier D R, Wang D. Genetic mapping of hepatocanalicular transporters establishes sister-P-glycoprotein (spgp) as a candidate for the major gallstone gene (Lith1) [abstract].  Hepatology . 1997;  26 358A
    CrossrefPubMedGoogle Scholar
  • 192 Wang D Q, Paigen B, Carey M C. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder bile.  J Lipid Res . 1997;  38 1395-1411
    CrossrefPubMedGoogle Scholar
  • 193 Cohen D E. Hepatocellular transport and secretion of biliary lipids.  Curr Opin Lipidol . 1999;  10 295-302
    CrossrefPubMedGoogle Scholar
  • 194 Lazaridis K N, Pham L, Tietz P. Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter.  J Clin Invest . 1997;  100 2714-2721
    PubMedGoogle Scholar
  • 195 Stravitz R T, Sanyal A J, Pandak W M. Induction of sodium-dependent bile acid transporter messenger RNA, protein, and activity in rat ileum by cholic acid.  Gastroenterology . 1997;  113 1599-1608
    PubMedGoogle Scholar
  • 196 Bolder U, Ton-Nu H-T, Schteingart C D. Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion.  Gastroenterology . 1997;  112 214-225
    PubMedGoogle Scholar
  • 197 Kubitz R, Wettstein M, Warskulat U. Regulation of the multidrug resistance protein 2 in the rat liver by lipopolysaccharide and dexamethasone.  Gastroenterology . 1999;  116 401-410
    CrossrefPubMedGoogle Scholar
  • 198 Rost D, Kartenbeck J, Keppler D. Changes in the localization of the rat canalicular conjugate export pump Mrp2 in phalloidin-induced cholestasis.  Hepatology . 1999;  29 814-821
    CrossrefPubMedGoogle Scholar
  • 199 Bossard R, Stieger B, O'Neill B. Ethinylestradiol treatment induces multiple canalicular membrane transport alterations in rat liver.  J Clin Invest . 1993;  91 2714-2720
    CrossrefPubMedGoogle Scholar
  • 200 Ito K, Suzuki H, Hirohashi T. Functional analysis of a canalicular multispecific organic anion transporter cloned from rat liver.  J Biol Chem . 1998;  273 1684-1688
    CrossrefPubMedGoogle Scholar
  • 201 Madon J, Eckhardt U, Gerloff T. Functional expression of the rat liver canalicular isoform of the multidrug resistance-associated protein.  FEBS Lett . 1997;  406 75-78
    CrossrefPubMedGoogle Scholar
  • 202 Buscher H P, Miltenberger C, MacNelly S. The histoautoradiographic localization of taurocholate in rat liver after bile duct ligation. Evidence for ongoing secretion and reabsorption processes.  J Hepatol . 1989;  8 181-191
    PubMedGoogle Scholar
  • 203 Böhme M, Müller M, Leier I. Cholestasis caused by inhibition of the adenosine triphosphate-dependent bile salt transport in rat liver.  Gastroenterology . 1994;  107 255-265
    PubMedGoogle Scholar
  • 204 Stieger B, Fattinger K, Madon J. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver.  Gastroenterology . 2000;  118 422-430
    CrossrefPubMedGoogle Scholar
  • 205 Stieger B, Zhang J, O'Neill B. Differential interaction of bile acids from patients with inborn errors of bile acid synthesis with hepatocellular bile acid transporters.  Eur J Biochem . 1997;  244 39-44
    CrossrefPubMedGoogle Scholar
  • 206 Yeh H Z, Schteingart C D, Hagey L R. Effect of side chain length on biotransformation, hepatic transport, and choleretic properties of chenodeoxycholyl homologues in the rodent: studies with dinorchenodeoxycholic acid, norchenodeoxycholic acid, and chenodeoxycholic acid.  Hepatology . 1997;  26 374-385
    CrossrefPubMedGoogle Scholar
  • 207 Dumont M, Uchman S, Erlinger S. Hypercholeresis induced by ursodeoxycholic acid and 7-ketolithocholic acid in the rat. Possible role of bicarbonate transport.  Gastroenterology . 1980;  79 82-89
    PubMedGoogle Scholar
  • 208 Kitani K, Kanai S. Effect of ursodeoxycholate on the bile flow in the rat.  Life Sci . 1982;  31 1973-1985
    CrossrefPubMedGoogle Scholar
  • 209 Hofmann A F. The cholehepatic circulation of unconjugated bile acids: an update. In: Paumgartner G, Stiehl A, Gerok W (eds). Bile acids and the hepatobiliary system Dordrecht: Kluwer Academic, 1993: 143-160
    Google Scholar
  • 210 Lamri Y, Erlinger S, Dumont M. Immunoperoxidase localization of ursodeoxycholic acid in rat biliary epithelial cells. Evidence for a cholehepatic circulation.  Liver . 1992;  12 351-354
    PubMedGoogle Scholar
  • 211 Kirkpatrick R B, Green M D, Hagey L R. Effect of side chain length on bile acid conjugation: glucuronidation, sulfation and coenzyme A formation of nor-bile acids and their natural C24 homologs by human and rat liver fractions.  Hepatology . 1988;  8 353-357
    PubMedGoogle Scholar
  • 212 Bolder U, Trang N V, Hagey L R. Sulindac is excreted into bile by a canalicular bile salt pump and undergoes a cholehepatic circulation in rats.  Gastroenterology . 1999;  117 962-971
    PubMedGoogle Scholar
  • 213 Rodriguez L AG, Williams R, Derby L E. Acute liver injury associated with nonsteroidal anti-inflammatory drugs and the role of risk factors.  Arch Intern Med . 1994;  154 311-316
    CrossrefPubMedGoogle Scholar
  • 214 Alpini G, Glaser S, Robertson W. Bile acids stimulate proliferative and secretory events in large but not small cholangiocytes.  Am J Physiol . 1997;  273 G518-G529
    PubMedGoogle Scholar
  • 215 Higgins D G, Thompson J D, Gibson T J. Using CLUSTAL for multiple sequence alignments.  Methods Enzymol . 1996;  266 383-402
    PubMedGoogle Scholar
  • 216 Page R D. TreeView: an application to display phylogenetic trees on personal computers.  Comput Appl Biosci . 1996;  12 357-358
    PubMedGoogle Scholar
  • 217 Dietmaier A, Gasser R, Graf J. Investigations on the sodium dependence of bile acid fluxes in the isolated perfused rat liver.  Biochim Biophys Acta . 1976;  443 81-91
    PubMedGoogle Scholar
  • 218 Poupon R, Chretien Y, Parquet M. Hepatic transport of bile acids in the isolated perfused rat liver.  Structure-kinetic relationship. Biochem Pharmacol . 1988;  37 209-212
    PubMedGoogle Scholar
  • 219 Iga T, Klaassen C D. Uptake of bile acids by isolated rat hepatocytes.  Biochem Pharmacol . 1982;  31 211-216
    CrossrefPubMedGoogle Scholar
  • 220 Ohkuma S, Kuriyama K. Uptake of cholic acid by freshly isolated rat hepatocytes: presence of a common carrier for bile acid transports.  Steroids . 1982;  39 7-19
    CrossrefPubMedGoogle Scholar
  • 221 Kuhn W F, Gewirtz D A. Stimulation of taurocholate and glycocholate efflux from the rat hepatocyte by arginine vasopressin.  Am J Physiol . 1988;  254 G732-G740
    PubMedGoogle Scholar
  • 222 Ziegler K, Frimmer M, Mullner S. Bile acid binding proteins in hepatocellular membranes of newborn and adult rats. Identification of transport proteins with azidobenzamidotauro[1 4C]cholate ([1 4C]ABATC).  Biochim Biophys Acta . 1989;  980 161-168
    PubMedGoogle Scholar
  • 223 Ohkuma S, Tamura J, Kuriyama K. Characteristics of cholic acid uptake in primary cultured hepatocytes.  Steroids . 1983;  42 205-215
    CrossrefPubMedGoogle Scholar
  • 224 Foellmann W, Petzinger E, Kinne R KH. Alterations of bile acid and bumetanide uptake during culturing of rat hepatocytes.  Am J Physiol . 1990;  258 C700-C712
    PubMedGoogle Scholar
  • 225 Deroubaix X, Coche T, Depiereux E. Saturation of hepatic transport of taurocholate in rats in vivo.  Am J Physiol . 1991;  260 G189-G196
    PubMedGoogle Scholar
  • 226 Montagnani M, Aldini R, Roda A. Species differences in hepatic bile acid uptake: comparative evaluation of taurocholate and tauroursodeoxycholate extraction in rat and rabbit.  Comp Biochem Physiol A Physiol . 1996;  113 157-164
    PubMedGoogle Scholar
  • 227 Schwarz L R, Burr R, Schwenk M. Uptake of taurocholic acid into isolated rat-liver cells.  Eur J Biochem . 1975;  55 617-623
    CrossrefPubMedGoogle Scholar
  • 228 Schwenk M, Schwarz L R. Preincubation accelerates taurocholate uptake into isolated liver cells.  Biochim Biophys Acta . 1981;  646 344-347
    PubMedGoogle Scholar
  • 229 Blitzer B L, Ratoosh S L, Donovan C B. Effects of inhibitors of Na+-coupled ion transport on bile acid uptake by isolated rat hepatocytes.  Am J Physiol . 1982;  243 G48-G53
    PubMedGoogle Scholar
  • 230 von Dippe P, Drain P, Levy D. Synthesis and transport characteristics of photoaffinaty probes for the hepatocyte bile and transport system.  J Biol Chem . 1983;  258 8890-8895
    PubMedGoogle Scholar
  • 231 Hardison W G, Bellentani S, Heasley V. Specificity of an Na+ -dependent taurocholate transport site in isolated rat hepatocytes.  Am J Physiol . 1984;  246 G477-G483
    PubMedGoogle Scholar
  • 232 Edmondson J W, Miller B A, Lumeng L. Effect of glucagon on hepatic taurocholate uptake: relationship to membrane potential.  Am J Physiol . 1985;  249 G427-G433
    PubMedGoogle Scholar
  • 233 Eaton D L, Richards J A. Kinetic evaluation of carrier-mediated transport of ouabain and taurocholic acid in isolated rat hepatocytes.  Evidence for independent transport systems. Biochem Pharmacol . 1986;  35 2721-2725
    PubMedGoogle Scholar
  • 234 Stacey N H, Kotecka B. Inhibition of taurocholate and ouabain transport in isolated rat hepatocytes by cyclosporin A.  Gastroenterology . 1988;  95 780-786
    PubMedGoogle Scholar
  • 235 Coche T, Deroubaix X, Depiereux E. Compartmental analysis of steady-state taurocholate transport kinetics by isolated rat hepatocytes.  Hepatology . 1991;  13 1203-1214
    CrossrefPubMedGoogle Scholar
  • 236 Sandker G W, Weert B, Olinga P. Characterization of transport in isolated human hepatocytes. A study with the bile acid taurocholic acid, the uncharged ouabain and the organic cations vecuronium and rocuronium.  Biochem Pharmacol . 1994;  47 2193-2200
    CrossrefPubMedGoogle Scholar
  • 237 Foliot A, Glaise D, Erlinger S. Long-term maintenance of taurocholate uptake by adult rat hepatocytes co-cultured with a liver epithelial cell line.  Hepatology . 1985;  5 215-219
    PubMedGoogle Scholar
  • 238 Larrauri A, Castell J V, Garrido G. S-adenosyl-L-methionine reverses the cholestatic effect of ethinylestradiol in rat hepatocytes by increasing its catabolism.  Cell Biol Toxicol . 1992;  8 13-26
    CrossrefPubMedGoogle Scholar
  • 239 Liang D, Hagenbuch B, Stieger B. Parallel decrease of Na+-taurocholate cotransport and its encoding mRNA in primary cultures of rat hepatocytes.  Hepatology . 1993;  18 1162-1166
    CrossrefPubMedGoogle Scholar
  • 240 Simon F R, Fortune J, Iwahashi M. Characterization of the mechanisms involved in the gender differences in hepatic taurocholate uptake.  Am J Physiol . 1999;  276 G556-G565
    PubMedGoogle Scholar
  • 241 Inoue M, Kinne R, Tran T. Taurocholate transport by rat liver sinusoidal membrane vesicles: evidence of sodium cotransport.  Hepatology . 1982;  2 572-579
    PubMedGoogle Scholar
  • 242 Ruifrok P G, Meijer D K. Sodium ion-coupled uptake of taurocholate by rat-liver plasma membrane vesicles.  Liver . 1982;  2 28-34
    PubMedGoogle Scholar
  • 243 Duffy M C, Blitzer B L, Boyer J L. Direct determination of the driving forces for taurocholate uptake into rat liver plasma membrane vesicles.  J Clin Invest . 1983;  72 1470-1481
    PubMedGoogle Scholar
  • 244 Simion F A, Fleischer B, Fleischer S. Two distinct mechanisms for taurocholate uptake in subcellular fractions from rat liver.  J Biol Chem . 1984;  259 10814-10822
    PubMedGoogle Scholar
  • 245 Blitzer B L, Donovan C B. A new method for the rapid isolation of basolateral plasma membrane vesicles from rat liver. Characterization, validation, and bile acid transport studies.  J Biol Chem . 1984;  259 9295-9301
    PubMedGoogle Scholar
  • 246 Suchy F J, Courchene S M, Blitzer B L. Taurocholate transport by basolateral plasma membrane vesicles isolated from developing rat liver.  Am J Physiol . 1985;  248 G648-G654
    PubMedGoogle Scholar
  • 247 Suchy F J, Bucuvalas J C, Goodrich A L. Taurocholate transport and Na+-K+-ATPase activity in fetal and neonatal rat liver plasma membrane vesicles.  Am J Physiol . 1986;  251 G665-G673
    PubMedGoogle Scholar
  • 248 Platte H-D, Honscha W, Schuh K. Functional characterization of the hepatic sodium-dependent taurocholate transporter stably transfected into an immortalized liver-derived cell line and V79 fibroblasts.  Eur J Cell Biol . 1996;  70 54-60
    PubMedGoogle Scholar
  • 249 Torchia E C, Shapiro R J, Agellon L B. Reconstitution of bile acid transport in the rat hepatoma McArdle RH-7777 cell line.  Hepatology . 1996;  24 206-211
    PubMedGoogle Scholar
  • 250 Schroeder A, Eckhardt U, Stieger B. Substrate specificity of the rat liver Na+-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells.  Am J Physiol . 1998;  274 G370-G375
    PubMedGoogle Scholar
  • 251 Bartholomew T C, Billing B H. The effect of 3-sulphation and taurine conjugation on the uptake of chenodeoxycholic acid by rat hepatocytes.  Biochim Biophys Acta . 1983;  754 101-109
    PubMedGoogle Scholar
  • 252 Hardison W G, Lowe P J, Gosink E. Nature of taurodehydrocholic acid uptake in rat hepatocytes.  Am J Physiol . 1988;  254 G269-G274
    PubMedGoogle Scholar
  • 253 Maglova L M, Jackson A M, Meng X J. Transport characteristics of three fluorescent conjugated bile acid analogs in isolated rat hepatocytes and couplets.  Hepatology . 1995;  22 637-647
    CrossrefPubMedGoogle Scholar
  • 254 Adachi Y, Kobayashi H, Kurumi Y. ATP-dependent taurocholate transport by rat liver canalicular membrane vesicles.  Hepatology . 1991;  14 655-659
    CrossrefPubMedGoogle Scholar
  • 255 Niinuma K, Kato Y, Suzuki H. Primary active transport of organic anions on bile canalicular membrane in humans.  Am J Physiol . 1999;  276 G1153-G1164
    PubMedGoogle Scholar
  • 256 Nishida T, Che M, Gatmaitan Z. Structure-specific inhibition by bile acids of adenosine triphosphate-dependent taurocholate transport in rat canalicular membrane vesicles.  Hepatology . 1995;  21 1058-1062
    CrossrefPubMedGoogle Scholar
  • 257 Azer S A, Stacey N H. Differential effects of cyclosporin A on the transport of bile acids by human hepatocytes.  Biochem Pharmacol . 1993;  46 813-819
    CrossrefPubMedGoogle Scholar
  • 258 Novak D A, Ryckman F C, Suchy F J. Taurocholate transport by basolateral plasma membrane vesicles isolated from human liver.  Hepatology . 1989;  10 447-453
    PubMedGoogle Scholar
  • 259 Kim R B, Leake B, Cvetkovic M. Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity.  J Pharmacol Exp Ther . 1999;  291 1204-1209
    PubMedGoogle Scholar
  • 260 Wolters H, Kuipers F, Slooff M J. Adenosine triphosphate-dependent taurocholate transport in human liver plasma membranes.  J Clin Invest . 1992;  90 2321-2326
    PubMedGoogle Scholar
      >