Purpose. To characterise in detail the patterns of expression and functional activities of CYP and efflux pump genes in Caco-2 cells stably transfected with human Pregnane X Receptor or murine Constitutive Androstane Receptor. Materials and Methods. Cell lines transfected with nuclear receptors were treated with established ligands, and gene expression of CYP and efflux pump genes were quantified by qRT-PCR and Western blot. P-glycoprotein activity was assessed by measuring calcein-AM accumulation and bidirectional permeability coefficients of digoxin and quinidine. CYP activities were measured with both fluorescent and non-fluorescent substrates. Results. hPXR and mCAR upregulated some CYP and efflux pump genes ligand dependently. P-glycoprotein level was increased, but CYP3A4 protein remained below the limit of detection. P-glycoprotein activity was markedly elevated in Caco/mCAR cells and more modestly in Caco/hPXR cells. CYP3A4 activity remained lower than that in vitamin D-treated Caco-2 cells. Conclusions. Nuclear receptors can modulate the expression of metabolic genes in Caco-2 cells, but the overall level of metabolism could not be efficiently controlled. P-glycoprotein activity increased, but CYP activities remained very low.
机构:
Fraunhofer Inst Toxicol & Expt Med, Ctr Drug Res & Med Biotechnol, D-30659 Hannover, GermanyFraunhofer Inst Toxicol & Expt Med, Ctr Drug Res & Med Biotechnol, D-30659 Hannover, Germany
Borlak, J
;
Zwadlo, C
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Fraunhofer Inst Toxicol & Expt Med, Ctr Drug Res & Med Biotechnol, D-30659 Hannover, GermanyFraunhofer Inst Toxicol & Expt Med, Ctr Drug Res & Med Biotechnol, D-30659 Hannover, Germany
机构:
Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
Cummins, CL
;
Jacobsen, W
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机构:
Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
Jacobsen, W
;
Benet, LZ
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Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
机构:
Fraunhofer Inst Toxicol & Expt Med, Ctr Drug Res & Med Biotechnol, D-30659 Hannover, GermanyFraunhofer Inst Toxicol & Expt Med, Ctr Drug Res & Med Biotechnol, D-30659 Hannover, Germany
Borlak, J
;
Zwadlo, C
论文数: 0引用数: 0
h-index: 0
机构:
Fraunhofer Inst Toxicol & Expt Med, Ctr Drug Res & Med Biotechnol, D-30659 Hannover, GermanyFraunhofer Inst Toxicol & Expt Med, Ctr Drug Res & Med Biotechnol, D-30659 Hannover, Germany
机构:
Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
Cummins, CL
;
Jacobsen, W
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h-index: 0
机构:
Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
Jacobsen, W
;
Benet, LZ
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA