Expression and distribution of CYP3A genes, CYP2B22, and MDR1, MRP1, MRP2, LRP efflux transporters in brain of control and rifampicin-treated pigs
| Autor: | Vincenzo Longo, Roberto Tolando, Francesco Rossignolo, Annalisa Nannelli, Paolo Rossato, Mario Pellegatti, P. Giovanni Gervasi |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty metabolism of xenobiotic CYP3A Swine Clinical Biochemistry Hippocampus Gene Expression ATP-binding cassette transporter Pharmacology Biology Cytochrome P-450 Enzyme System In vivo Internal medicine Gene expression medicine Animals Cytochrome P-450 CYP3A Tissue Distribution ATP Binding Cassette Transporter Subfamily B Member 1 Molecular Biology Antibiotics Antitubercular citocromo P450 Pregnane X receptor Multidrug resistance-associated protein 2 suino Brain Membrane Transport Proteins Transporter Cell Biology General Medicine tessuto cerebrale trasportatori Multidrug Resistance-Associated Protein 2 Endocrinology Liver Steroid Hydroxylases Multidrug Resistance-Associated Proteins Rifampin |
| Zdroj: | Molecular and cellular biochemistry 337 (2010): 133–143. doi:10.1007/s11010-009-0292-1 info:cnr-pdr/source/autori:Nannelli A., Rossignolo F., Tolando R., Rossato P., Pellegatti M., Longo V., Gervasi P. G./titolo:Expression and distribution of CYP3A genes, CYP2B22, and MDR1, MRP1, MRP2, LRP efflux transporters in brain of control and rifampicin-treated pigs/doi:10.1007%2Fs11010-009-0292-1/rivista:Molecular and cellular biochemistry/anno:2010/pagina_da:133/pagina_a:143/intervallo_pagine:133–143/volume:337 |
| ISSN: | 1573-4919 |
| DOI: | 10.1007/s11010-009-0292-1 |
| Popis: | The in vivo effect of rifampicin, a potent ligand of PXR, on gene expression of CYP2B22, 3A22, 3A29, 3A46, CAR, PXR and MDR1, MRP1, MRP2, LRP transporters in liver and cortex, cerebellum, midbrain, hippocampus, meninges and brain capillaries of pig was investigated. Animals were treated i.p. with four daily doses of rifampicin (40 mg/kg). The basal mRNA expressions of the individual CYP3As, CYP2B22, CAR, and PXR in various brain regions, except meninges, were about or below 10% of the corresponding hepatic mRNA values, whereas the mRNAs of brain transporters were closer or comparable to those in liver. After pig treatment with rifampicin, the mRNA expression of CYPs and transporters from brain regions did not appear to change, except CYP3A22 and 3A29 in cortex and hippocampus, CYP2B22 in meninges. An enzymatic analysis for CYP3As and CYP2B, in microsomes and mitochondria from liver and brain tissues using the marker activities 7-benzyloxyquinoline O-debenzylase and the anthraldehyde oxidase, showed the lack of rifampicin induction in all the brain regions, unlike liver. Taken together, our results demonstrate that CYP2B22, CYP3As, and MDR1, MRP1, MRP2, and LRP transporters are all expressed, although at different extent, in the brain regions but, despite the presence of PXR and CAR, are resistant to induction indicating that the regulation of these proteins is more complex in brain than in liver. These data obtained in vivo in the brain regions and liver of pig may be of interest to human metabolism in CNS. |
| Databáze: | OpenAIRE |
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