AJP - GI Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 272: G1285-G1303, 1997;
0193-1857/97 $5.00
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Muller, M.
Right arrow Articles by Jansen, P. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Muller, M.
Right arrow Articles by Jansen, P. L.

AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 6 1285-G1303, Copyright © 1997 by American Physiological Society

ARTICLES

Molecular aspects of hepatobiliary transport

M. Muller and P. L. Jansen
Department of Medicine, University Hospital Groningen, The Netherlands.

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.


This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
F. R. Simon, M. Iwahashi, L.-J. Hu, I. Qadri, I. M. Arias, D. Ortiz, R. Dahl, and E. Sutherland
Hormonal regulation of hepatic multidrug resistance-associated protein 2 (Abcc2) primarily involves the pattern of growth hormone secretion
Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G595 - G608.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
M. Trauner and J. L. Boyer
Bile Salt Transporters: Molecular Characterization, Function, and Regulation
Physiol Rev, April 1, 2003; 83(2): 633 - 671.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
S. Perwaiz, D. Forrest, D. Mignault, B. Tuchweber, M. J. Phillip, R. Wang, V. Ling, and I. M. Yousef
Appearance of atypical 3{alpha},6{beta},7{beta},12{alpha}-tetrahydroxy-5{beta}-cholan-24-oic acid in spgp knockout mice
J. Lipid Res., March 1, 2003; 44(3): 494 - 502.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
P. Boileau, C. Wolfrum, D. Q. Shih, T.-A. Yang, A. W. Wolkoff, and M. Stoffel
Decreased Glibenclamide Uptake in Hepatocytes of Hepatocyte Nuclear Factor-1{alpha}-Deficient Mice: A Mechanism for Hypersensitivity to Sulfonylurea Therapy in Patients With Maturity-Onset Diabetes of the Young, Type 3 (MODY3)
Diabetes, December 1, 2002; 51(90003): S343 - 348.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
P Milkiewicz, M G Roma, E Elias, and R Coleman
Hepatoprotection with tauroursodeoxycholate and {beta} muricholate against taurolithocholate induced cholestasis: involvement of signal transduction pathways
Gut, July 1, 2002; 51(1): 113 - 119.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Kobayashi, N. Ohshiro, A. Shibusawa, T. Sasaki, S. Tokuyama, T. Sekine, H. Endou, and T. Yamamoto
Isolation, Characterization and Differential Gene Expression of Multispecific Organic Anion Transporter 2 in Mice
Mol. Pharmacol., July 1, 2002; 62(1): 7 - 14.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Nagata, H. Kusuhara, H. Endou, and Y. Sugiyama
Expression and Functional Characterization of Rat Organic Anion Transporter 3 (rOat3) in the Choroid Plexus
Mol. Pharmacol., May 1, 2002; 61(5): 982 - 988.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Hasegawa, H. Kusuhara, D. Sugiyama, K. Ito, S. Ueda, H. Endou, and Y. Sugiyama
Functional Involvement of Rat Organic Anion Transporter 3 (rOat3; Slc22a8) in the Renal Uptake of Organic Anions
J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 746 - 753.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
G. Lee, S. Dallas, M. Hong, and R. Bendayan
Drug Transporters in the Central Nervous System: Brain Barriers and Brain Parenchyma Considerations
Pharmacol. Rev., December 1, 2001; 53(4): 569 - 596.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
N. Morita, H. Kusuhara, T. Sekine, H. Endou, and Y. Sugiyama
Functional Characterization of Rat Organic Anion Transporter 2 in LLC-PK1 Cells
J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1179 - 1184.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. Nakai, R. Nakagomi, Y. Furuta, T. Tokui, T. Abe, T. Ikeda, and K. Nishimura
Human Liver-Specific Organic Anion Transporter, LST-1, Mediates Uptake of Pravastatin by Human Hepatocytes
J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 861 - 867.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
D. W. A. Beno, M. R. Uhing, M. Goto, Y. Chen, V. A. Jiyamapa-Serna, and R. E. Kimura
Endotoxin-induced reduction in biliary indocyanine green excretion rate in a chronically catheterized rat model
Am J Physiol Gastrointest Liver Physiol, May 1, 2001; 280(5): G858 - G865.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. H. Cha, T. Sekine, J.-i. Fukushima, Y. Kanai, Y. Kobayashi, T. Goya, and H. Endou
Identification and Characterization of Human Organic Anion Transporter 3 Expressing Predominantly in the Kidney
Mol. Pharmacol., April 16, 2001; 59(5): 1277 - 1286.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
E. S. Ward, G. M. Pollack, and K. L. R. Brouwer
Probenecid-Associated Alterations in Valproate Glucuronide Hepatobiliary Disposition: Mechanistic Assessment Using Mathematical Modeling
J. Pharmacol. Exp. Ther., April 1, 2001; 297(1): 141 - 147.
[Abstract] [Full Text]

Home page
 Mol. Cell. Biol.Home page
F. M. Rausa, Y. Tan, H. Zhou, K. W. Yoo, D. B. Stolz, S. C. Watkins, R. R. Franks, T. G. Unterman, and R. H. Costa
Elevated Levels of Hepatocyte Nuclear Factor 3beta in Mouse Hepatocytes Influence Expression of Genes Involved in Bile Acid and Glucose Homeostasis
Mol. Cell. Biol., November 1, 2000; 20(21): 8264 - 8282.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Renal Physiol.Home page
U. Karbach, J. Kricke, F. Meyer-Wentrup, V. Gorboulev, C. Volk, D. Loffing-Cueni, B. Kaissling, S. Bachmann, and H. Koepsell
Localization of organic cation transporters OCT1 and OCT2 in rat kidney
Am J Physiol Renal Physiol, October 1, 2000; 279(4): F679 - F687.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
A. Yokota, M. Veenstra, P. Kurdi, H. W. van Veen, and W. N. Konings
Cholate Resistance in Lactococcus lactis Is Mediated by an ATP-Dependent Multispecific Organic Anion Transporter
J. Bacteriol., September 15, 2000; 182(18): 5196 - 5201.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
G. L. Scheffer, M. Kool, M. Heijn, Marcel de Haas, A. C. L. M. Pijnenborg, J. Wijnholds, A. van Helvoort, M. C. de Jong, J. H. Hooijberg, C. A. A. M. Mol, et al.
Specific Detection of Multidrug Resistance Proteins MRP1, MRP2, MRP3, MRP5, and MDR3 P-Glycoprotein with a Panel of Monoclonal Antibodies
Cancer Res., September 1, 2000; 60(18): 5269 - 5277.
[Abstract] [Full Text]

Home page
 Drug Metab. Dispos.Home page
Y. Liu, E. R. Bacon, K. Ballinger, C. D. V. Black, K. Illig, G. L. McIntire, P. P. Wang, N. O'Neil, L. Kinter, and V. C. Desai
Pharmacokinetics and Hepatic Disposition of Bis[1-(ethoxycarbonyl)propyl]5-acetylamino-2,4,6-triiodoisophthalate in Rats and Isolated Perfused Rat Livers
Drug Metab. Dispos., July 1, 2000; 28(7): 731 - 736.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Renal Physiol.Home page
A. Pavlova, H. Sakurai, B. Leclercq, D. R. Beier, A. S. L. Yu, and S. K. Nigam
Developmentally regulated expression of organic ion transporters NKT (OAT1), OCT1, NLT (OAT2), and Roct
Am J Physiol Renal Physiol, April 1, 2000; 278(4): F635 - F643.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. J. Dresser, A. T. Gray, and K. M. Giacomini
Kinetic and Selectivity Differences between Rodent, Rabbit, and Human Organic Cation Transporters (OCT1)
J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 1146 - 1152.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
K. Ogawa, H. Suzuki, T. Hirohashi, T. Ishikawa, P. J. Meier, K. Hirose, T. Akizawa, M. Yoshioka, and Y. Sugiyama
Characterization of inducible nature of MRP3 in rat liver
Am J Physiol Gastrointest Liver Physiol, March 1, 2000; 278(3): G438 - G446.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
N. Ballatori, J. F. Rebbeor, G. C. Connolly, D. J. Seward, B. E. Lenth, J. H. Henson, P. Sundaram, and J. L. Boyer
Bile salt excretion in skate liver is mediated by a functional analog of Bsep/Spgp, the bile salt export pump
Am J Physiol Gastrointest Liver Physiol, January 1, 2000; 278(1): G57 - G63.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
R. Masereeuw, S. A. Terlouw, R. A. M. H. van Aubel, F. G. M. Russel, and D. S. Miller
Endothelin B Receptor-Mediated Regulation of ATP-Driven Drug Secretion in Renal Proximal Tubule
Mol. Pharmacol., January 1, 2000; 57(1): 59 - 67.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
V. Gorboulev, C. Volk, P. Arndt, A. Akhoundova, and H. Koepsell
Selectivity of the Polyspecific Cation Transporter rOCT1 Is Changed by Mutation of Aspartate 475 to Glutamate
Mol. Pharmacol., December 1, 1999; 56(6): 1254 - 1261.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
N. Ballatori, D. N. Hager, S. Nundy, D. S. Miller, and J. L. Boyer
Carrier-mediated uptake of lucifer yellow in skate and rat hepatocytes: a fluid-phase marker revisited
Am J Physiol Gastrointest Liver Physiol, October 1, 1999; 277(4): G896 - G904.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. J. Soroka, M. K. Pate, and J. L. Boyer
Canalicular Export Pumps Traffic with Polymeric Immunoglobulin A Receptor on the Same Microtubule-associated Vesicle in Rat Liver
J. Biol. Chem., September 10, 1999; 274(37): 26416 - 26424.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
H. Ishizuka, K. Konno, T. Shiina, H. Naganuma, K. Nishimura, K. Ito, H. Suzuki, and Y. Sugiyama
Species Differences in the Transport Activity for Organic Anions across the Bile Canalicular Membrane
J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1324 - 1330.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
H. Gutmann, G. Fricker, J. Drewe, M. Toeroek, and D. S. Miller
Interactions of HIV Protease Inhibitors with ATP-Dependent Drug Export Proteins
Mol. Pharmacol., August 1, 1999; 56(2): 383 - 389.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
J.-i. Nishino, H. Suzuki, D. Sugiyama, T. Kitazawa, K. Ito, M. Hanano, and Y. Sugiyama
Transepithelial Transport of Organic Anions across the Choroid Plexus: Possible Involvement of Organic Anion Transporter and Multidrug Resistance-Associated Protein
J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 289 - 294.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
T. Abe, M. Kakyo, T. Tokui, R. Nakagomi, T. Nishio, D. Nakai, H. Nomura, M. Unno, M. Suzuki, T. Naitoh, et al.
Identification of a Novel Gene Family Encoding Human Liver-specific Organic Anion Transporter LST-1
J. Biol. Chem., June 11, 1999; 274(24): 17159 - 17163.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Kusuhara, T. Sekine, N. Utsunomiya-Tate, M. Tsuda, R. Kojima, S. H. Cha, Y. Sugiyama, Y. Kanai, and H. Endou
Molecular Cloning and Characterization of a New Multispecific Organic Anion Transporter from Rat Brain
J. Biol. Chem., May 7, 1999; 274(19): 13675 - 13680.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
A. F. Hofmann
Bile Acids: The Good, the Bad, and the Ugly
Physiology, February 1, 1999; 14(1): 24 - 29.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Y. Kato, S. Akhteruzzaman, A. Hisaka, and Y. Sugiyama
Hepatobiliary Transport Governs Overall Elimination of Peptidic Endothelin Antagonists in Rats
J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 568 - 574.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Akhteruzzaman, Y. Kato, A. Hisaka, and Y. Sugiyama
Primary Active Transport of Peptidic Endothelin Antagonists by Rat Hepatic Canalicular Membrane
J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 575 - 581.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
X.-Y. Chu, H. Suzuki, K. Ueda, Y. Kato, S.-I. Akiyama, and Y. Sugiyama
Active Efflux of CPT-11 and Its Metabolites in Human KB-Derived Cell Lines
J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 735 - 741.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
F. R. Simon, J. Fortune, M. Iwahashi, S. Bowman, A. Wolkoff, and E. Sutherland
Characterization of the mechanisms involved in the gender differences in hepatic taurocholate uptake
Am J Physiol Gastrointest Liver Physiol, February 1, 1999; 276(2): G556 - G565.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
H. Ishizuka, K. Konno, H. Naganuma, K. Nishimura, H. Kouzuki, H. Suzuki, B. Stieger, P. J. Meier, and Y. Sugiyama
Transport of Temocaprilat into Rat Hepatocytes: Role of Organic Anion Transporting Polypeptide
J. Pharmacol. Exp. Ther., October 1, 1998; 287(1): 37 - 42.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
C. A. Hinchman, J. F. Rebbeor, and N. Ballatori
Efficient hepatic uptake and concentrative biliary excretion of a mercapturic acid
Am J Physiol Gastrointest Liver Physiol, October 1, 1998; 275(4): G612 - G619.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. F. HAMM-ALVAREZ and M. P. SHEETZ
Microtubule-Dependent Vesicle Transport: Modulation of Channel and Transporter Activity in Liver and Kidney
Physiol Rev, October 1, 1998; 78(4): 1109 - 1129.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
R. A. M. H. v. Aubel, M. A. v. Kuijck, J. B. Koenderink, P. M. T. Deen, C. H. v. Os, and F. G. M. Russel
Adenosine Triphosphate-Dependent Transport of Anionic Conjugates by the Rabbit Multidrug Resistance-Associated Protein Mrp2 Expressed in Insect Cells
Mol. Pharmacol., June 1, 1998; 53(6): 1062 - 1067.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
T. Gerloff, B. Stieger, B. Hagenbuch, J. Madon, L. Landmann, J. Roth, A. F. Hofmann, and P. J. Meier
The Sister of P-glycoprotein Represents the Canalicular Bile Salt Export Pump of Mammalian Liver
J. Biol. Chem., April 17, 1998; 273(16): 10046 - 10050.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
W. Geng, A. J. Schwab, T. Horie, C. A. Goresky, and K. S. Pang
Hepatic Uptake of Bromosulfophthalein-Glutathione in Perfused Eisai Hyperbilirubinemic Mutant Rat Liver: A Multiple-Indicator Dilution Study
J. Pharmacol. Exp. Ther., February 1, 1998; 284(2): 480 - 492.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
F. Garcia, A. Kierbel, M. C. Larocca, S. A. Gradilone, P. Splinter, N. F. LaRusso, and R. A. Marinelli
The Water Channel Aquaporin-8 Is Mainly Intracellular in Rat Hepatocytes, and Its Plasma Membrane Insertion Is Stimulated by Cyclic AMP
J. Biol. Chem., April 6, 2001; 276(15): 12147 - 12152.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. R. Kast, B. Goodwin, P. T. Tarr, S. A. Jones, A. M. Anisfeld, C. M. Stoltz, P. Tontonoz, S. Kliewer, T. M. Willson, and P. A. Edwards
Regulation of Multidrug Resistance-associated Protein 2 (ABCC2) by the Nuclear Receptors Pregnane X Receptor, Farnesoid X-activated Receptor, and Constitutive Androstane Receptor
J. Biol. Chem., January 18, 2002; 277(4): 2908 - 2915.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
V. S. Zinchuk, T. Okada, K. Akimaru, and H. Seguchi
Asynchronous expression and colocalization of Bsep and Mrp2 during development of rat liver
Am J Physiol Gastrointest Liver Physiol, March 1, 2002; 282(3): G540 - G548.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online