Cited by 226Drug Transport and Resistance MechanismsLiver physiology and pathologyDrug-Induced Hepatotoxicity and Protection

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Biliary excretion in primary rat hepatocytes cultured in a collagen-sandwich configuration

Liu, Xingrong, LeCluyse, Edward L., Brouwer, Kenneth R., Gan, Liang-Sheng L., Lemasters, John J., Stieger, Bruno, Meier, Peter J., Brouwer, Kim L. R.·1999·American Journal of Physiology-Gastrointestinal and Liver Physiology

DOI 10.1152/ajpgi.1999.277.1.g12

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Abstract

The objective of the present investigation was to examine the functional reestablishment of polarity in freshly isolated hepatocytes cultured between 2 layers of gelled collagen (sandwich configuration). Immunoblot analysis demonstrated that the canalicular multispecific organic anion transport protein (multidrug resistance-associated protein, Mrp2) was partially maintained in day 5 hepatocytes cultured in a sandwich configuration. Fluorescein-labeled taurocholate and carboxydichlorofluorescein were excreted into and concentrated in the bile canalicular lumen of day 5sandwich-cultured hepatocytes, resulting in formation of fluorescent networks in standard buffer (intact bile canaliculi). Confocal microscopy studies demonstrated that 1) carboxydichlorofluorescein that had concentrated in the canalicular lumen was released into the incubation buffer in the presence of Ca 2+ -free buffer (disrupted bile canaliculi), and 2) rhodamine-dextran, an extracellular space marker, was only able to diffuse into the canalicular lumen in the presence of Ca 2+ -free buffer. The cumulative uptake of [ 3 H]taurocholate in day 5 sandwich-cultured hepatocytes was significantly higher in standard buffer compared with Ca 2+ -free buffer, due to accumulation of taurocholate in canalicular spaces. When [ 3 H]taurocholate was preloaded in the day 5sandwich-cultured hepatocytes, taurocholate efflux was greater in Ca 2+ -free compared with standard buffer. The biliary excretion index of taurocholate, equivalent to the percentage of retained taurocholate in the canalicular networks, increased from ∼8% at day 0 to ∼60% at day 5 in sandwich-cultured hepatocytes. In summary, hepatocytes cultured in a collagen-sandwich configuration for up to 5 days establish intact canalicular networks, maintain Mrp2, reestablish polarized excretion of organic anions and bile acids, and represent a useful in vitro model system to investigate the hepatobiliary disposition of substrates.

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Hepatobiliary Disposition of Troglitazone and Metabolites in Rat and Human Sandwich-Cultured Hepatocytes: Use of Monte Carlo Simulations to Assess the Impact of Changes in Biliary Excretion on Troglitazone Sulfate Accumulation
Lee, J. K., Marion, T. L., Abe, K., Lim, C., Pollock, G. M., & Brouwer, K. L. R. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.156653 · Cited by 57
“…hepatocyte culture because the cells repolarize, regain their proper morphology, and maintain liver-specific metabolic activity, including stable expression of cytochrome P450 enzymes over longer times (Liu et al., 1998, 1999a,b,c; Hamilton et al., 2001; Hewitt et al., 2007; Mingoia et al., 2007).”
BackgroundMethodInfluentialSelf-citation
Contribution of High Basolateral Bile Salt Efflux to the Lack of Hepatotoxicity in Rat in Response to Drugs Inducing Cholestasis in Human
Jemnitz, K., Veres, Z., & Vereczkey, L. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq044 · Cited by 57
“Human and rat SCH are commonly used to estimate the biliary efflux of compounds and also to assess hepatotoxic potential of drugs due to interaction with biliary efflux processes (Kemp and Brouwer 2004; Liu et al., 1999).”
Background
Advancements in Microphysiological systems: Exploring organoids and organ-on-a-chip technologies in drug development -focus on pharmacokinetics related organs-
Kimura, H., Nishikawa, M., Kutsuzawa, N., Tokito, F., Kobayashi, T., Kurniawan, D. A., Shioda, H., Cao, W., Shinha, K., Nakamura, H., et al. (2024) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2024.101046 · Cited by 63
Effect of Culture Time on the Basal Expression Levels of Drug Transporters in Sandwich-Cultured Primary Rat Hepatocytes
Tchaparian, E. H., Houghton, J. S., Uyeda, C., Grillo, M. P., & Jin, L. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.039545 · Cited by 56
“They are extensively used as an experimental model to investigate metabolism, transport, and hepatotoxicity of investigational drugs (Liu et al., 1999; Ansede et al., 2010).”
Background
Identification of cytoskeletal [14C]carboplatin-binding proteins reveals reduced expression and disorganization of actin and filamin in cisplatin-resistant cell lines.
Shen, D., Liang, X., Gawinowicz, M. A., & Gottesman, M. M. (2004) · PubMed · doi:10.1124/mol.66.4 · Cited by 31
“Well preserved liver-specific functions in sandwich-cultured rat hepatocytes make this a valuable in vitro model to study the expression and function of transport proteins, and predict in vivo hepatobiliary clearance (Liu et al., 1999a).”
BackgroundMethodInfluentialSelf-citation
Inhibition of Human Hepatic Bile Acid Transporters by Tolvaptan and Metabolites: Contributing Factors to Drug-Induced Liver Injury?
Slizgi, J. R., Lu, Y., Brouwer, K. R., St. Claire, R. L., Freeman, K. M., Pan, M., Brock, W. J., & Brouwer, K. L. R. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfv231 · Cited by 53
“The biliary excretion index (BEI) was calculated according to the following equation (Liu et al., 1999a): BEIð%Þ ¼ AccumulationStandard HBSS AccumulationCa2þ free HBSS AccumulationStandard HBSS 100 The in vitro biliary clearance (Clbiliary) was determined using the following equation (Ghibellini et…”
MethodSelf-citation
Effect of culture conditions on the expression and function of Bsep, Mrp2, and Mdr1a/b in sandwich-cultured rat hepatocytes
Turncliff, R. Z., Tian, X., & Brouwer, K. L. R. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.02.004 · Cited by 53
Self-citation
Regulation of Multidrug Resistance-Associated Protein 2 by Calcium Signaling in Mouse Liver
da Cruz, L. N., Guerra, M. T., Kruglov, E. A., Mennone, A., Garcia, C. R. S., Chen, J., & Nathanson, M. H. (2010) · Hepatology · doi:10.1002/hep.23625 · Cited by 53
“This cell system was used because it preserves structural and functional polarity of hepatocytes.(37,38) CMFDA accumulated in the canalicular lumen of hepatocytes (Fig.”
Method
Bile canalicular dynamics in hepatocyte sandwich cultures
Reif, R., Karlsson, J., Günther, G., Beattie, L., Wrangborg, D., Hammad, S., Begher‐Tibbe, B., Damle‐Vartak, A., Melega, S., Kaye, P. M., et al. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1575-9 · Cited by 50
“Assays to measure hepatobiliary excretion of bile acids and chemical compounds have been established (Bi et al. 2006; Kostrubsky et al. 2003; Liu et al. 1999c).”
Background
Confocal Imaging with a Fluorescent Bile Acid Analogue Closely Mimicking Hepatic Taurocholate Disposition
Bruyn, T. D., Sempels, W., Snoeys, J., et al. (2014) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23933 · Cited by 52
Self-citation
Liver Cell Culture Techniques
Castell, J. V., & Gómez-Lechón, M. J. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-201-4_4 · Cited by 51
Mechanistic Modeling of Pitavastatin Disposition in Sandwich-Cultured Human Hepatocytes: A Proteomics-Informed Bottom-Up Approach
Vildhede, A. M., Mateus, A., Khan, E. K., et al. (2016) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.066746 · Cited by 51
“Time-dependent disposition of pitavastatin in SCHHs was assessed using a method adapted from the originators to the B-CLEAR technology (Qualyst Transporter Solutions, Research Triangle Park, NC) (Liu et al., 1999).”
Method
Prediction of Pharmacokinetic Drug-Drug Interactions Using Human Hepatocyte Suspension in Plasma and Cytochrome P450 Phenotypic Data. III. In Vitro-in Vivo Correlation with Fluconazole
Lu, C., Berg, C., Prakash, S. R., et al. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.019000 · Cited by 51
The Design of In Vitro Liver Sinusoid Mimics Using Chitosan–Hyaluronic Acid Polyelectrolyte Multilayers
Kim, Y.-H., Larkin, A. L., Davis, R. M., et al. (2010) · Tissue Engineering Part A · doi:10.1089/ten.tea.2009.0695 · Cited by 49
“35,36 The presence of canaliculi was determined through the localization of a ﬂuorescent di-peptyl peptidase IV enzyme.”
MULTIPLE TRANSPORT SYSTEMS MEDIATE THE HEPATIC UPTAKE AND BILIARY EXCRETION OF THE METABOLICALLY STABLE OPIOID PEPTIDE [d-PENICILLAMINE2,5]ENKEPHALIN
Hoffmaster, K. A., Zamek‐Gliszczynski, M. J., Pollack, G. M., & Brouwer, K. L. R. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.104.001420 · Cited by 47
Self-citation
Knocking Down Breast Cancer Resistance Protein (Bcrp) by Adenoviral Vector-Mediated RNA Interference (RNAi) in Sandwich-Cultured Rat Hepatocytes: A Novel Tool To Assess the Contribution of Bcrp to Drug Biliary Excretion
Yue, W., Abe, K., & Brouwer, K. L. R. (2008) · Molecular Pharmaceutics · doi:10.1021/mp800100e · Cited by 45
Self-citation
IMMORTALIZATION OF HUMAN HEPATOCYTES BY TEMPERATURE-SENSITIVE SV40 LARGE-T ANTIGEN
Smalley, M. J., Leiper, K. A., Tootle, R., McCloskey, P., O'Hare, M. J., & Hodgson, H. J. F. (2001) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1290/1071-2690(2001)037 · Cited by 21
Self-citation
Toxicity and intracellular accumulation of bile acids in sandwich-cultured rat hepatocytes: Role of glycine conjugates
Chatterjee, S., Bijsmans, I. T. G. W., van Mil, S. W. C., Augustijns, P., & Annaert, P. (2013) · Toxicology in Vitro · doi:10.1016/j.tiv.2013.10.020 · Cited by 44
Role of AMP-activated protein kinase α1 in 17α-ethinylestradiol-induced cholestasis in rats
Li, X., Liu, R., Luo, L., Yu, L., Chen, X., Sun, L., Wang, T., Hylemon, P. B., Zhou, H., Jiang, Z., et al. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1697-8 · Cited by 44
“Rat primary hepatocytes were isolated by a twostep collagenase perfusion method and cultured in a collagen-sandwich configuration as reported previously (Liu et al. 1999).”
Method
Involvement of Organic Cation Transporters in the Kinetics of Trimethylamine N-oxide
Miyake, T., Mizuno, T., Mochizuki, T., Kimura, M., Matsuki, S., Irie, S., Ieiri, I., Maeda, K., & Kusuhara, H. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.04.067 · Cited by 44
Optimization of culture conditions for determining hepatobiliary disposition of taurocholate in sandwich-cultured rat hepatocytes
Chandra, P., LeCluyse, E. L., & Brouwer, K. L. R. (2001) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/bf02577575 · Cited by 44
“This polarized excretion confirms that intact canalicular networks were formed in the sandwich-cultured hepatocytes (Liu et al., 1999b).”
BackgroundMethodInfluentialSelf-citation
Experimental Conditions That Influence the Utility of 2′7′-Dichlorodihydrofluorescein Diacetate (DCFH2-DA) as a Fluorogenic Biosensor for Mitochondrial Redox Status
de Haan, L. R., Reiniers, M. J., Reeskamp, L. F., Belkouz, A., Ao, L., Cheng, S., Ding, B., van Golen, R. F., & Heger, M. (2022) · Antioxidants · doi:10.3390/antiox11081424 · Cited by 46
“DCFH2-DA is converted to DCF at a higher rate in DMEM compared to RPMI 1640 medium [31,68], so the primary hepatocytes were exposed to more DCF and less DCFH2-DA than the HepG2 cells.”
MethodInfluential
Use of cassette dosing in sandwich-cultured rat and human hepatocytes to identify drugs that inhibit bile acid transport
Wolf, K., Vora, S., Webster, L. O., Generaux, G. T., Polli, J. W., & Brouwer, K. L. R. (2009) · Toxicology in Vitro · doi:10.1016/j.tiv.2009.08.009 · Cited by 43
“…IH -PA Author M anuscript N IH -PA Author M anuscript min/kg) of taurocholate were calculated using B-CLEAR® technology (Qualyst, Inc., Raleigh, NC; Liu et al., 1999a) and the following equations: (1) (2) where substrate accumulation in cells+bile was determined in hepatocytes preincubated in…”
BackgroundMethodInfluentialSelf-citation
Culture density contributes to hepatic functions of fresh human hepatocytes isolated from chimeric mice with humanized livers: Novel, long-term, functional two-dimensional in vitro tool for developing new drugs
Yamasaki, C., Ishida, Y., Yanagi, A., Yoshizane, Y., Kojima, Y., Ogawa, Y., Kageyama, Y., Iwasaki, Y., Ishida, S., Chayama, K., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0237809 · Cited by 42
“This observation indicated that in the presence of Ca the integrity of the bile canalicular networks remains intact, while in the absence of Ca2 the integrity of the canalicular space is disrupted, causing leakage of the canalicular contents, as reported previously [29].”
Result
Differential Modulation of Cytochrome P450 Activity and the Effect of 1-Aminobenzotriazole on Hepatic Transport in Sandwich-Cultured Human Hepatocytes
Kimoto, E., Walsky, R. L., Zhang, H., Bi, Y., Whalen, K. M., Yang, Y.-S., Linder, C. D., Xiao, Y., Iseki, K., Fenner, K. S., et al. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.039297 · Cited by 42
“The initial uptake rate was calculated from the slope between 0.5 and 5 min, whereas biliary clearance was estimated as previously reported (Liu et al., 1999b).”
BackgroundMethodInfluential
Emodin alleviates hepatic steatosis by inhibiting sterol regulatory element binding protein 1 activity by way of the calcium/calmodulin‐dependent kinase kinase–AMP‐activated protein kinase–mechanistic target of rapamycin–p70 ribosomal S6 kinase signaling pathway
Wang, S., Li, X., Guo, H., Yuan, Z., Wang, T., Zhang, L., & Jiang, Z. (2016) · Hepatology Research · doi:10.1111/hepr.12788 · Cited by 42
Biliary efflux transporters involved in the clearance of rosuvastatin in sandwich culture of primary rat hepatocytes
Jemnitz, K., Veres, Z., Tugyi, R., & Vereczkey, L. (2009) · Toxicology in Vitro · doi:10.1016/j.tiv.2009.10.009 · Cited by 42
Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors
Saran, C., Sundqvist, L., Ho, H. S. S., Niskanen, J., Honkakoski, P., & Brouwer, K. L. R. (2021) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.121.000828 · Cited by 44
“Following a 24-hour exposure to TKIs (day 5), the biliary excretion index was measured using B-CLEAR technology (Brouwer et al., 2013; Liu et al., 1999; Swift et al., 2010).”
MethodSelf-citation
Recent Progress in Hepatocyte Culture Models and Their Application to the Assessment of Drug Metabolism, Transport, and Toxicity in Drug Discovery: The Value of Tissue Engineering for the Successful Development of a Microphysiological System
Tetsuka, K., Ohbuchi, M., & Tabata, K. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.05.010 · Cited by 42
Quantification of Drug-Induced Inhibition of Canalicular Cholyl-l-Lysyl-Fluorescein Excretion From Hepatocytes by High Content Cell Imaging
Barber, J., Stahl, S. H., Summers, C., Barrett, G., Park, B. K., Foster, J. R., & Kenna, J. G. (2015) · Toxicological Sciences · doi:10.1093/toxsci/kfv159 · Cited by 39
Heparin hydrogel sandwich cultures of primary hepatocytes
Foster, E. E., You, J., Siltanen, C. A., Patel, D., Haque, A., Anderson, L., & Revzin, A. (2015) · European Polymer Journal · doi:10.1016/j.eurpolymj.2014.12.033 · Cited by 38
In Vivo Biliary Clearance Should Be Predicted by Intrinsic Biliary Clearance in Sandwich-Cultured Hepatocytes
Nakakariya, M., Ono, M., Amano, N., et al. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.042101 · Cited by 38
“…the biliary clearance of some drugs, such as angiotensin II receptor blockers, HMG-CoA reductase inhibitors, and -lactam antibiotics, showed correlation between sandwich-cultured rat or human hepatocytes and in vivo (Liu et al., 1999a; Abe et al., 2008, 2009; Fukuda et al., 2008; Li et al., 2010).”
BackgroundMethodInfluential
Characterization of Chemically Induced Hepatotoxicity in Collagen Sandwiches of Rat Hepatocytes
Farkas, D., & Tannenbaum, S. R. (2005) · Toxicological Sciences · doi:10.1093/toxsci/kfi145 · Cited by 37
Regulation of Human Hepatic Drug Transporter Activity and Expression by Diesel Exhaust Particle Extract
Vée, M. L., Jouan, E., Stieger, B., Lecureur, V., & Fardel, O. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121232 · Cited by 39
“Biliary excretion index (BEI) reflecting canalicular secretion of taurocholate was calculated using the following equation [47]:”
MethodSelf-citation
Constrained spheroids for prolonged hepatocyte culture
Tong, W. H., Fang, Y., Yan, J., Hong, X., Singh, N. H., Wang, S. R., Nugraha, B., Xia, L., Fong, E. L. S., Iliescu, C., et al. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.11.036 · Cited by 36
“For example, the current in vitro gold standard, the collagen sandwich culture system, has been shown to be capable of reestablishing and maintaining polarity in primary rat hepatocytes for up to 5 days [58, 69].”
Background
Viability assessment in sandwich-cultured rat hepatocytes after xenobiotic exposure
Kemp, D. C., & Brouwer, K. L. R. (2004) · Toxicology in Vitro · doi:10.1016/j.tiv.2004.04.014 · Cited by 36
Self-citation
Interaction of eight HIV protease inhibitors with the canalicular efflux transporter ABCC2 (MRP2) in sandwich‐cultured rat and human hepatocytes
Ye, Z., Camus, S., Augustijns, P., & Annaert, P. (2010) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.701 · Cited by 36
Retention of Transporter Activities in Cryopreserved, Isolated Rat Hepatocytes
Houle, R., Raoul, J., Lévesque, J.-F., et al. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.4.447 · Cited by 35
“In this model the billiary efflux transporters such as MRP2 are maintained, however, uptake transporters such as NTCP are significantly down-regulated (Liu et al., 1999).”
Background
Hepatocyte function within a stacked double sandwich culture plate cylindrical bioreactor for bioartificial liver system
Lei, X., Arooz, T., Zhang, S., Tuo, X., Xiao, G., Susanto, T. A. K., Sundararajan, J., Cheng, T., Kang, Y., Poh, H. J., et al. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.06.078 · Cited by 35
Differential methotrexate hepatotoxicity on rat hepatocytes in 2-D monolayer culture and 3-D gel entrapment culture
Yin, J. B., Meng, Q., Zhang, G., & Sun, Y. (2009) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2009.04.004 · Cited by 35
In vitro model systems to investigate bile salt export pump (BSEP) activity and drug interactions: A review
Cheng, Y., Woolf, T. F., Gan, J., & He, K. (2015) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2015.11.029 · Cited by 34
Hepatobiliary Disposition of 17-OHPC and Taurocholate in Fetal Human Hepatocytes: A Comparison with Adult Human Hepatocytes
Sharma, S., Ellis, E. C. S., Gramignoli, R., Dorko, K., Tahan, V., Hansel, M. C., Mattison, D. R., Caritis, S. N., Hines, R. N., Venkataramanan, R., et al. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.044891 · Cited by 34
“A large BEI (as high as taurocholate) indicates extensive excretion of substrate into the canalicular space via transporters (Liu et al., 1999).”
BackgroundMethodInfluential
Hepatobiliary Disposition of a Drug/Metabolite Pair: Comprehensive Pharmacokinetic Modeling in Sandwich-Cultured Rat Hepatocytes
Turncliff, R., Hoffmaster, K. A., Kalvass, J., Pollack, G. M., & Brouwer, K. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.102616 · Cited by 34
Self-citation
Alpha-naphthylisothiocyanate modulates hepatobiliary transporters in sandwich-cultured rat hepatocytes
Guo, C., He, L., Yao, D., Aa, J., Cao, B., Ren, J., Wang, G., & Pan, G. (2013) · Toxicology Letters · doi:10.1016/j.toxlet.2013.09.019 · Cited by 32
Primary hepatocyte cultures as prominentin vitrotools to study hepatic drug transporters
Ramboer, E., Vanhaecke, T., Rogiers, V., & Vinken, M. (2013) · Drug Metabolism Reviews · doi:10.3109/03602532.2012.756010 · Cited by 32
Multidrug Resistance Protein 2-Mediated Estradiol-17β-d-glucuronide Transport Potentiation: In Vitro-in Vivo Correlation and Species Specificity
Herédi‐Szabó, K., Glavinas, H., Kis, E.-É., et al. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.023895 · Cited by 32
“tocytes were performed by the modified method of Liu et al. (1999). In brief,”
Method

Authors: Liu, X., LeCluyse, E. L., Brouwer, K. R., Gan, L.-S. L., Lemasters, J. J., Stieger, B., Meier, P. J., & Brouwer, K. L. R.
Affiliations: Division of Drug Delivery and Disposition, School of Pharmacy, and
Division of Bioanalysis and Drug Metabolism, Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709; and
University of North Carolina at Chapel Hill (US)
University Hospital Zurich (CH)
ORCID: Liu, Xingrong
LeCluyse, Edward L.
Lemasters, John J.
Stieger, Bruno
Brouwer, Kim L. R.
Venue: American Journal of Physiology-Gastrointestinal and Liver Physiology
Publisher: American Physiological Society
Published: 1999-07-01
Volume: 277
Issue: 1
Pages: G12-G21
ISSN: 0193-1857 (ISSN-L)
1522-1547
DOI: 10.1152/ajpgi.1999.277.1.g12
OpenAlex: W2101528448
Semantic Scholar: 501c1cfc2938afc5aa6a1bdf0351de034d80a0bc
Cited by: 226
References: 30
Citations by year: 2026: 2 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 9 · 2015: 16 · 2014: 12 · 2013: 21 · 2012: 11
FWCI: 1.56
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (R01GM041935, GM 41935)
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords: biliary excretion, hepatocyte polarity, MRP2, taurocholate, bile canaliculi, organic anion transport, bile acid efflux
MeSH terms: Animals, Bile, Carrier Proteins, Cell Membrane, Cells, Cultured, Collagen, Cytological Techniques, Fluoresceins, Liver, Male, Taurocholic Acid, Time Factors, Immunoblotting, Cell Polarity, Rats, Wistar, Anion Transport Proteins, Rats

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Biliary excretion in primary rat hepatocytes cultured in a collagen-sandwich configuration

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