Regulation of mRNA Expression of MDR1, MRP1, MRP2 and MRP3 by Prototypical Microsomal Enzyme Inducers in Primary Cultures of Human and Rat Hepatocytes
The mRNA induction of various transporters by rifampicin (Rif), dexamethasone (Dex) and omeprazole (Ome) was investigated in primary cultures of cryopreserved human and rat hepatocytes. Analysis was performed by quantitative realtime RTPCR using primers and TaqMan probes. In primary cultures of hu...
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Published in | DRUG METABOLISM AND PHARMACOKINETICS Vol. 21; no. 4; pp. 297 - 307 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
01.01.2006
Japanese Society for the Study of Xenobiotics |
Subjects | |
Online Access | Get full text |
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Summary: | The mRNA induction of various transporters by rifampicin (Rif), dexamethasone (Dex) and omeprazole (Ome) was investigated in primary cultures of cryopreserved human and rat hepatocytes. Analysis was performed by quantitative realtime RTPCR using primers and TaqMan probes. In primary cultures of human hepatocytes, mRNA levels of MDR and MRP1 were increased by about 1.5 fold and 1.3 fold, respectively, by exposure to Rif at 2 to 50μM as compared with 0.1% DMSOtreated controls. MRP2 mRNA levels in the same human hepatocytes were significantly increased by 1.2 to 1.8 fold by exposure to Rif at 50μM as compared with controls. In primary cultures of rat hepatocytes, Mdr1a and Mdr1b mRNA levels were not increased or only slightly increased at 24hr by exposure to any of the inducers at 2, 10 or 50μM. Mrp2 mRNA levels in the same rat hepatocytes were significantly increased by 7 to 45 fold by exposure to Dex at 2μM as compared with controls. Based on the species differences observed in the present study, primary cultures of cryopreserved hepatocytes from both the human and rat should be useful in preclinical drug development for evaluating candidate drugs for transporter induction. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1347-4367 1880-0920 |
DOI: | 10.2133/dmpk.21.297 |