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  • 1
    Keywords: brain ; RECEPTOR ; CELLS ; tumor ; Germany ; human ; SYSTEM ; SITE ; GENE ; PROTEIN ; RELEASE ; kidney ; LINKAGE ; TRANSPORT ; NERVOUS-SYSTEM ; resistance ; MUTATIONS ; LOCALIZATION ; MULTIDRUG-RESISTANCE PROTEIN ; ATP-dependent transport ; CONJUGATE EXPORT PUMP ; SUBSTRATE-SPECIFICITY ; GLIOMAS ; EFFLUX ; DISORDERS ; RE ; VESICLES ; CEREBELLAR NEURONS ; BASOLATERAL HEPATOCYTE MEMBRANE ; human brain ; BINDING CASSETTE TRANSPORTER ; multidrug resistance protein ; function ; DEHYDROEPIANDROSTERONE-SULFATE ; de-hydroepiandrosterone 3-sulfate ; GABA(A) receptor modulation ; GABA-A RECEPTOR ; multidrug resistance proteins ; NEUROACTIVE STEROIDS ; neuron ; neurosteroids ; paroxysmal kinesigenic choreoathetosis ; MULTIDRUG-RESISTANCE-PROTEIN
    Abstract: Dehydroepiandrosterone 3-sulfate and other neurosteroids are synthesized in the CNS and peripheral nervous system where they may modulate neuronal excitability by interacting with ligand-gated ion channels. For this modulatory activity, neurosteroids have to be locally released from either neurons or glial cells. We here identify the integral membrane protein ABCC11 (multidrug resistance protein 8) as an ATP-dependent efflux pump for steroid sulfates, including dehydroepiandrosterone 3-sulfate, and localize it to axons of the human CNS and peripheral nervous system. ABCC11 mRNA was detected in human brain by real-time polymerase chain reaction. Antibodies raised against ABCC11 served to detect the protein in brain by immunoblotting and immunofluorescence microscopy. ABCC11 was preferentially found in the white matter of the brain and co-localized with neurofilaments indicating that it is an axonal protein. Additionally, ABCC11 was localized to axons of the peripheral nervous system. For functional studies, ABCC11 was expressed in polarized Madin-Darby canine kidney cells where it was sorted to the apical membrane. This apical sorting is in accordance with the localization of ABCC11 to the axonal membrane of neurons. Inside-out plasma membrane vesicles containing recombinant ABCC11 mediated ATP-dependent transport of dehydroepiandrosterone 3-sulfate with a K-m value of 21 mu M. This transport function together with the localization of the ABCC11 protein in vicinity to GABAA receptors is consistent with a role of ABCC11 in dehydroepiandrosterone 3-sulfate release from neurons to sites of dehydroepiandrosterone 3-sulfate-mediated receptor modulation. Our findings may provide a basis for the characterization of mutations in the human ABCC11 gene and their linkage with neurological disorders. (c) 2005 Published by Elsevier Ltd on behalf of IBRO
    Type of Publication: Journal article published
    PubMed ID: 16359813
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  • 2
    Keywords: RECEPTOR ; Germany ; IN-VIVO ; KINASE ; MODEL ; MODELS ; TYROSINE KINASE ; GENE ; GENE-EXPRESSION ; MICE ; PATIENT ; DOMAIN ; CONTRAST ; BIOLOGY ; MOLECULAR-BIOLOGY ; MATURATION ; STIMULATION ; MOUSE ; MUTANT ; NO ; resistance ; MUTATION ; genetics ; REGION ; REGIONS ; MUTATIONS ; MUSCLE ; PHENOTYPE ; SKELETAL-MUSCLE ; MOUSE MODEL ; REVEALS ; heredity ; ARCHITECTURE ; molecular biology ; molecular ; ADULT ; RE ; PATTERN ; WEIGHT ; DEFECTS ; MUTANTS ; GENOTYPE ; NERVE ; ENGLAND ; NOV ; ACETYLCHOLINE-RECEPTORS ; CONTRACTION ; DOK7 ; INNERVATION ; KINASE DOMAIN ; KINASE MUSK ; SYNAPSE FORMATION
    Abstract: In the muscle-specific tyrosine kinase receptor gene MUSK, a heteroallelic missense and a null mutation were identified in a patient suffering from a congenital myasthenic syndrome (CMS). We generated one mouse line carrying the homozygous missense mutation V789M in musk (musk(V789M/V789M) mice) and a second hemizygous line, resembling the patient genotype, with the V789M mutation on one allele and an allele lacking the kinase domain (musk(V789M/-) mice). We report here that musk(V789M/V789M) mice present no obvious abnormal phenotype regarding weight, muscle function and viability. In contrast, adult musk(V789M/-) mice suffer from severe muscle weakness, exhibit shrinkage of pelvic and scapular regions and hunchback. Musk(V789M/-) diaphragm develops less force upon direct or nerve-induced stimulation. A profound tetanic fade is observed following nerve-evoked muscle contraction, and fatigue resistance is severely impaired upon a train of tetanic nerve stimulations. Electrophysiological measurements indicate that fatigable muscle weakness is due to impaired neurotransmission as observed in a patient suffering from a CMS. The diaphragm of adult musk(V789M/-) mice exhibits pronounced changes in endplate architecture, distribution and innervation pattern. Thus, the missense mutation V789M in MuSK acts as a hypomorphic mutation and leads to insufficiency in MuSK function in musk(V789M/-) mutants. These mutant mice represent valuable models for elucidating the roles of MuSK for synapse formation, maturation and maintenance as well as for studying the pathophysiology of a CMS due to MuSK mutations
    Type of Publication: Journal article published
    PubMed ID: 18718936
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  • 3
    Keywords: CELLS ; CELL ; Germany ; human ; TOOL ; CDNA ; GENE ; PROTEIN ; DOMAIN ; tumour ; hepatocytes ; FREQUENCY ; polymorphism ; POLYMORPHISMS ; VARIANTS ; TRANSPORT ; IDENTIFICATION ; RAT-LIVER ; GLUTATHIONE ; resistance ; UP-REGULATION ; MEMBRANE ; MUTATION ; HEPATOCYTE CANALICULAR ISOFORM ; DRUG-RESISTANCE ; MULTIDRUG-RESISTANCE ; ATP-dependent transport ; SUBSTRATE-SPECIFICITY ; VARIANT ; FUNCTIONAL-CHARACTERIZATION ; ANION TRANSPORT ; basolateral membrane,cholestasis,hepatocellular transporters,MRP3,polymorphism,SNP ; BINDING CASSETTE ; CHRONIC CONJUGATED HYPERBILIRUBINEMIA ; DUBIN-JOHNSON-SYNDROME
    Abstract: The human multidrug resistance protein 3 (MRP3, symbol ABCC3) is an ATP-binding cassette transporter that mediates the efflux of organic anions, including lipophilic substances conjugated with glucuronate, sulphate or glutathione, across the basolateral membrane of polarized cells (e.g. hepatocytes) into blood. Genetic variants of MRP3 may affect the transport of these substances out of cells. The aims of this study were: (i) to identify MRP3 polymorphisms; (ii) to functionally characterize one relatively frequent MRP3 polymorphism; and (iii) to establish whether MRP3 transports bilirubin glucuronosides. Exonic nucleotide variants in the ABCC3 gene were identified by single-strand conformation polymorphism analysis. The 3890G〉A mutation, resulting in MRP3-Arg(1297) His, was introduced into the ABCC3 cDNA which was stably transfected into MDCKII cells. For the functional characterization of MRP3-Arg(1297) His in comparison with MRP3, ATP-dependent transport was analysed in isolated membrane vesicles. Two non- synonymous MRP3 variants were identified with an allele frequency of 0.003 for 1643T〉A (MRP3-Leu(148)Gln) and 0.08 for 3890G〉A (MRP3-Arg(1297) His). Because of the high, frequency of the 3890G〉A mutation, and because of the close proximity of Arg(1297) to the second nucleotide-binding domain, we pursued the functional characterization of the MRP3-Arg(1297)His polymorphic variant. MRP3-Arg(1297)His was correctly localized to the basolateral membrane of polarized MDCKII cells. We identified monoglucuronosyl bilirubin, bisgiucuronosyl bilirubin and leukotriene C-4 as substrates for both MRP3 and MRP3-Arg(1297)His. Dehydroepiandrosterone-3-sulphate and 17beta-glucuronosyl oestradiol were transported with similar kinetics by MRP3 and MRP3-Arg(1297) His. This experimental setup provides a useful tool to analyse the functional consequences of polymorphic variants of MRP3. Pharmacogenetics 14: 213-223 (C) 2004 Lippincott Williams Wilkins
    Type of Publication: Journal article published
    PubMed ID: 15083066
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  • 4
    Keywords: brain ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; tumor ; CELL ; Germany ; human ; MICROSCOPY ; PROTEIN ; PROTEINS ; SAMPLE ; SAMPLES ; DRUG ; FAMILY ; MEMBER ; MEMBERS ; GLYCOPROTEIN ; NO ; GLUTATHIONE ; resistance ; MEMBRANE ; NUCLEOTIDES ; REGION ; REGIONS ; LOCALIZATION ; POLYMERASE-CHAIN-REACTION ; CHAIN-REACTION ; DRUG-RESISTANCE ; MULTIDRUG-RESISTANCE ; CONJUGATE EXPORT PUMP ; ORGANIC ANION TRANSPORTER ; CHAIN ; quantitative polymerase chain reaction ; ADULT ; polymerase chain reaction ; P-GLYCOPROTEIN ; TRANSPORTER ; NEURONS ; GLYCOPROTEINS ; BASOLATERAL HEPATOCYTE MEMBRANE ; blood-brain barrier ; CEREBROSPINAL FLUID BARRIER ; CULTURED RAT ASTROCYTES ; human brain ; MICROVESSEL ENDOTHELIAL-CELLS ; MRP4 CONFERS RESISTANCE ; multidrug resistance proteins (MRPs,symbol ABCC) ; NORMAL HUMAN-TISSUES ; organic anions
    Abstract: Multidrug resistance proteins (MRPs, symbol ABCC) are membrane glycoproteins that mediate the ATP-dependent export of organic anions, including cytotoxic and antiviral drugs, from cells. To identify MRP family members possibly involved in the intrinsic resistance of human brain to cytotoxic and antiviral drugs, we analyzed the expression and localization of MRP1-MRP6 in rapidly frozen perilesional samples of several regions of adult human brain obtained during neurosurgery. Quantitative polymerase chain reaction analysis showed expression of MRP1, MRP2, MRP3, MRP4, and MRP5 mRNA, whereas MRP6 mRNA was below detectability. However, immunofluorescence microscopy of cryosections from human brain showed no reactivity for the MRP2 or MRP3 proteins. The proteins MRP1, MRP4, and MRP5 were clearly localized by confocal laser scanning microscopy to the luminal side of brain capillary endothelial cells. The MRP4 and MRP5 proteins were also detected in astrocytes of the subcortical white matter. Notably, MRP5 protein was present in pyramidal neurons. MRP proteins may, thus, contribute to the cellular efflux of endogenous anionic glutathione or glucuronate conjugates (substrates for MRP1), cyclic nucleotides (substrates for MRP4 and MRP5), or glutathione (co-substrate for MRP1 and MRP4); in addition, they may play an important role in the resistance of the brain to several cytotoxic and antiviral drugs. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15501592
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  • 5
    Keywords: CANCER ; EXPRESSION ; tumor ; carcinoma ; Germany ; DEATH ; PROTEIN ; PROTEINS ; TISSUE ; TUMORS ; PATIENT ; MECHANISM ; FAMILY ; MALIGNANCIES ; resistance ; chemotherapy ; LOCALIZATION ; SUPERFAMILY ; Jun ; adenocarcinoma ; QUANTITATIVE-ANALYSIS ; drug resistance ; DRUG-RESISTANCE ; MULTIDRUG-RESISTANCE ; pancreatic cancer ; pancreatic carcinoma ; CONJUGATE EXPORT PUMP ; SUBSTRATE-SPECIFICITY ; ONCOLOGY-GROUP ; PHASE-II ; multidrug resistance ; MALIGNANCY ; PANCREATIC-CANCER ; DUCTAL ADENOCARCINOMA ; P-GLYCOPROTEIN ; TRANSPORTER ; BASOLATERAL HEPATOCYTE MEMBRANE ; multidrug resistance protein ; TISSUE SAMPLES ; MRP3 ; ABCC family ; CYCLIC-NUCLEOTIDES ; INDUCIBLE EXPRESSION ; MDR1 ; MRP ; NORMAL HUMAN TISSUES
    Abstract: Pancreatic ductal adenocarcinoma is among the top 10 causes of death from cancer in industrialized countries. In comparison with other gastrointestinal malignancies, pancreatic cancer is one of the tumors most resistant to chemotherapy. An important mechanism of tumor multidrug resistance is increased drug efflux mediated by several transporters of the ABC superfamily. Especially BCRP (ABCG2), MDR1 P-glycoprotein (ABCB1) and members of the MRP (ABCC) family are important in mediating drug resistance. The MRP family consists of 9 members (MRP1-MRP9) with MRP1-MRP6 being best characterized with respect to protein localization and substrate selectivity. Here, we quantified the mRNA expression of BCRP and of all MRP family members in normal human pancreas and pancreatic carcinoma and analyzed the mRNA level of the transporters most abundantly expressed in pancreatic tissue, BCRP, MRP1, MRP3, MRP4 and MRP5, in 37 tissue samples. In addition, we determined the localization of the 4 MRP proteins in normal human pancreas and in pancreatic carcinoma. The expression of BCRP, MRP1 and MRP4 mRNA did not correlate with tumor stage or grading. On the other hand, the expression of MRP3 mRNA was upregulated in pancreatic carcinoma samples and was correlated with tumor grading. The MRP5 mRNA level was significantly higher in pancreatic carcinoma tissue compared to normal pancreatic tissue. These data suggest that MRP3 and MRP5 are involved in drug resistance of pancreatic tumors and that quantitative analysis of their expression may contribute to predict the benefit of chemotherapy in patients with pancreatic cancer. © 2005 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15688370
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  • 6
    Keywords: EXPRESSION ; tumor ; Germany ; human ; MICROSCOPY ; SUPPORT ; liver ; primary ; hepatocytes ; DOWN-REGULATION ; ASSOCIATION ; ISOFORM ; STAGE ; UP-REGULATION ; DECREASE ; MEMBRANE ; LOCALIZATION ; MULTIDRUG-RESISTANCE PROTEIN ; HUMAN LIVER ; ORGANIZATION ; ABCC2 ; CONJUGATE EXPORT PUMP ; MRP2 ; ELIMINATION ; HUMAN-LIVER ; CANALICULAR MEMBRANES ; CHOLESTATIC RAT-LIVER ; CROSS-LINKING ; OBSTRUCTIVE CHOLESTASIS ; organic anion transporters,radixin,multidrug resistance protein,primary biliary cirrhosis,immunofluo
    Abstract: Background/Aims: Expression and localization of human hepatocellular transporters and of radixin, cross-linking actin with some membrane transporters, may change in cholestatic liver diseases.Methods: We investigated the uptake transporters OATP2 (SLC21A6), OATP8 (SLC21A8), and NTCP (SLC10A1), the export pumps MRP2 (ABCC2), MRP3 (ABCC3), MRP6 (ABCC6), and P-glycoproteins (ABCB1, ABCB4, ABCB11), and radixin, in non-icteric primary biliary cirrhosis (PBC stages I-III) and control human liver needle-biopsies using immunofluorescence microscopy and semi-quantitative RT-PCR.Results: Expression and localization of all transporters were unchanged in PBC I-II. Immunostaining intensities of uptake transporters decreased in PBC III with a concomitant decrease in mRNA levels. Immunostaining intensities and mRNA levels of export pumps were similar in controls and PBC I-III, however, irregular MRP2 immunostaining suggested redistribution of MRP2 into intracellular structures in PBC III. Areas of irregular MRP2 immunostaining showed largely reduced radixin immunostaining, whereas normal hepatocytes had MRP2 and radixin confined to the canalicular membrane. Disrupted localization of radixin and MRP2 supports the concept that radixin contributes to the canalicular localization of MRP2.Conclusions: Down-regulation of uptake transporters may contribute to the impaired hepatobiliary elimination in advanced PBC, and partially altered localization of MRP2 may reflect the onset of changes leading to icteric PBC. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 14568249
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  • 7
    Keywords: CELLS ; tumor ; CELL ; Germany ; human ; liver ; CDNA ; GENE ; GENES ; PROTEIN ; PROTEINS ; DRUG ; RAT ; SEQUENCE ; FREQUENCY ; polymorphism ; POLYMORPHISMS ; VARIANTS ; ACID ; NUCLEIC-ACIDS ; TRANSPORT ; IDENTIFICATION ; DIFFERENCE ; MEMBRANE ; MUTATION ; DATABASE ; MUTATIONS ; LOCALIZATION ; HEPATIC-UPTAKE ; HUMAN LIVER ; SUBSTRATE-SPECIFICITY ; ELIMINATION ; VARIANT ; databases ; TRANSPORTER ; C SLC21A6 ; hepatobiliary transport ; OATP1B3 ; OATP8 ; organic anion transport ; POLYPEPTIDES
    Abstract: Objective Hepatocellular uptake transporters are involved in the hepatobiliary elimination of endogenous and xenobiotic substances. Mutations in genes encoding these uptake transporters may be key determinants of interindividual variability in hepatobiliary elimination and drug disposition. Our aim was to investigate the functional consequences of mutations in the SLCO1B3 gene encoding the hepatic uptake transporter for organic anions OATP1B3, formerly termed OATP8. Methods Mutations occurring in Caucasian Europeans and observed in databases were introduced into the SLCO1B3 cDNA and the consequences were analyzed in stably transfected canine MDCKII cells and human HEK293 cells. The functional consequences were examined for two frequent polymorphisms SLCO1B3-334T〉G, encoding OATP1B3-S112A (allelic frequency of 74%) and SLCO1B3-699G〉A, encoding OATP1B3-M233I (allelic frequency of 71%) and one rare polymorphism SLCO1B3-1564G〉T, encoding OATP1B3-G522C (allelic frequency of 1.9%) and one artificial mutation SLCO1B3-1748G〉A, encoding OATP1B3-G583E. Results: OATP1B3-S112A, OATP1B3-M233I, and the OATP1B3 protein corresponding to the reference sequence (accession NM_019844), showed a comparable lateral localization in stably transfected MDCKII cells, whereas OATP1B3-G522C and OATP1B3-G583E proteins were retained intracellularly. Both latter amino acid substitutions abolished the transport of bile acids mediated by OATP1B3, whereas other substrates, like bromosulfophthalein, were transported by all polymorphic variants of the protein. Conclusions The functional consequences of three polymorphisms and one artificial mutation include differences in the localization and in transport characteristics of several OATP1B3 proteins. This study demonstrates the importance of the analysis of genetic variations in genes encoding transport proteins for the understanding of individual variations in the hepatobiliary elimination of substances. (C) 2004 Lippincott Williams Wilkins
    Type of Publication: Journal article published
    PubMed ID: 15226676
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  • 8
    Keywords: brain ; CANCER ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; tumor ; AGENTS ; Germany ; human ; MICROSCOPY ; neoplasms ; GENE ; GENES ; PROTEIN ; PROTEINS ; DRUG ; TUMORS ; FAMILY ; CELL-LINES ; MEMBERS ; TRANSPORT ; resistance ; MEMBRANE ; PCR ; DELIVERY ; LOCALIZATION ; PHENOTYPE ; MULTIDRUG-RESISTANCE ; GLIOMAS ; chemoresistance ; multidrug resistance ; SUBCELLULAR-LOCALIZATION ; AGENT ; ONCOLOGY ; RE ; BRAIN-TUMORS ; GLIOMA ; endothelial cells ; P-GLYCOPROTEIN ; TRANSPORTER ; SUBTYPE ; BASOLATERAL HEPATOCYTE MEMBRANE ; MRP4 CONFERS RESISTANCE ; LEVEL ; SUBTYPES ; EFFLUX PUMPS ; immunofluorescence ; membrane transport proteins ; MICROVESSEL ENDOTHELIUM ; multidrug resistance protein ; MULTIDRUG-RESISTANCE PROTEINS ; oligoastrocytoma ; oligodendroglioma ; RAT ASTROCYTES ; SUBFAMILY
    Abstract: Delivery of therapeutic agents to the brain and its neoplasms depends on the presence of membrane transport proteins in the blood-brain barrier and in the target cells. The cellular and subcellular localization of these membrane transporters determines the drug accessibility to the brain and its tumors. We therefore analyzed the expression and localization of six members of the multidrug resistance protein family of ATP-dependent efflux pumps (ABCCI-ABCC6, formerly MRPI-MRP6) and of six organic anion uptake transporters (OATPIA2, OATP1B1, OATP1B3, OATP1C1, OAT2B1, and OATP4A1) in 61 human glioma specimens of different histologic subtypes. Real-thine PCRs indicated expressions of ABCO, ABCC3, ABCC4, and ABCC5. In addition, we detected expressions of the OATP uptake transporter genes SLCOIA2, SWO1C1, SLCO2B1, and SLC04A1. At. the protein level, however, only OATPIA2 and OATP2B1 were detectable by immunofluorescence microscopy in the luminal membrane of endothelial cells forming the blood-brain barrier and the blood-tumor barrier, but not in the glioma cells. ABCC4 and ABCC5 proteins were the major ABCC subfamily members in gliomas, localized both at the luminal side of the endothetial cells and in the glioma cells of astrocytic tumors and in the astrocytic portions of oligoastrocytomas. These results indicate that expression of ABCC4 and ABCC5 is associated with an astrocytic phenotype, in accordance with their expression in astrocytes and with the higher chemoresistance of astrocytic tumors as compared with oligodendrogliomas. Our data provide a basis for the assessment of the role of uptake transporters and efflux pumps in the accessibility of human gliomas for chemotherapeutic agents
    Type of Publication: Journal article published
    PubMed ID: 16357150
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  • 9
    Keywords: PEPTIDE ; SPECTRA ; CELLS ; INHIBITOR ; Germany ; human ; INFORMATION ; PROTEIN ; DRUG ; kidney ; FAMILY ; hepatocytes ; PRIMARY CULTURES ; TRANSPORT ; IDENTIFICATION ; GLUTATHIONE ; resistance ; MEMBRANE ; LINE ; POLYPEPTIDE ; MULTIDRUG-RESISTANCE PROTEIN ; HUMAN LIVER ; DRUG-RESISTANCE ; MULTIDRUG-RESISTANCE ; CONJUGATE EXPORT PUMP ; SUBSTRATE-SPECIFICITY ; HUMAN HEPATOCYTES ; multidrug resistance ; INHIBITORS ; RE ; secretion ; TRANSPORTER ; hepatobiliary transport ; NEED ; multidrug resistance protein ; TRANSCELLULAR TRANSPORT ; VECTORIAL TRANSPORT ; APICAL MEMBRANE ; OATP1B3 OATP8
    Abstract: Hepatobiliary elimination of many organic anions is initiated by OATP1B1 (OATP2, LST-1, OATP-C), OATP1B3 (OATP8), and OATP2B1 (OATP-B), which are the predominant uptake transporters of human hepatocytes. Thereafter, the unidirectional efflux pump ABCC2 (multidrug resistance protein 2) mediates the transport of organic anions, including glutathione conjugates and glucuronosides, into bile. In this study, we generated a Madin-Darby canine kidney (MDCKII) cell line stably expressing recombinant OATP1B1, OATP1B3, and OATP2B1 in the basolateral membrane and ABCC2 in the apical membrane. Double-transfected MDCKII cells stably expressing ABCC2 together with OATP1B1, OATP1B3, or OATP2B1 served as control cells. The quadruple-transfected cells exhibited high rates of vectorial transport of organic anions, including bromosulfophthalein, cholecystokinin peptide (CCK-8), and estrone 3-sulfate. The quadruple-transfected cells enabled the identification of substrates for uptake or vectorial transport that may be missed in studies with a double-transfected cell line, as exemplified by CCK-8, which is a substrate for OATP1B3 but not for OATP1B1 or OATP2B1. The broad substrate spectrum covered by the three hepatocellular OATP transporters enables representative analyses of the uptake of many organic anions into human hepatocytes. The broad spectrum of organic anions transported vectorially by the quadruple-transfected cells also provides valuable information on the substrate selectivity of ABCC2, without the need for studies in inside-out membrane vesicles containing the ABCC2 protein. The quadruple-transfected MDCKII-ABCC2/OATP1B1/1B3/2B1 cells may thus be useful for the identification of substrates and inhibitors, including drug candidates, undergoing uptake and secretion by human hepatocytes, under conditions that may be better defined than in primary cultures of human hepatocytes
    Type of Publication: Journal article published
    PubMed ID: 16046661
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