Physiological regulation of P-glycoprotein, MRP1, MRP2 and cytochrome P450 3A2 during rat ontogeny
| Autor: | Luigi Candussio, A.M. Rosati, Tullio Giraldi, Silvia Maniori, Fiora Bartoli, Giuliana Decorti |
|---|---|
| Přispěvatelé: | Rosati, A., Maniori, S., Decorti, Giuliana, Candussio, Luigi, Giraldi, Tullio, Bartoli, Fiora |
| Rok vydání: | 2003 |
| Předmět: |
Aging
ATP-Binding Cassette Transporter Ontogeny Wistar N-Demethylating Western blot P glycoprotein MRP1 MRP2 ontogeny Cytochrome P-450 CYP3A medicine Animals ATP Binding Cassette Transporter Subfamily B Member 1 Rats Wistar P-glycoprotein biology medicine.diagnostic_test ATP-Binding Cassette Transporters Aryl Hydrocarbon Hydroxylases Carrier Proteins Embryo Mammalian Liver Organ Specificity Oxidoreductases P-Glycoprotein Rats Reverse Transcriptase Polymerase Chain Reaction Animal Multidrug resistance-associated protein 2 Aryl Hydrocarbon Hydroxylase Cytochrome P450 Oxidoreductases N-Demethylating Cell Biology Embryo Mammalian Molecular biology Real-time polymerase chain reaction Oxidoreductase biology.protein Rat Carrier Protein Developmental Biology |
| Zdroj: | Development, growthdifferentiation. 45(4) |
| ISSN: | 0012-1592 |
| Popis: | P-glycoprotein and the multidrug resistance-related proteins MRP1 and MRP2 belong to the ATP binding cassette family of proteins and transport a wide range of substrates. These proteins are also involved in metabolic and excretory processes of xenobiotics. The rat genes mdr1a and mdr1b code for P-glycoproteins, while mrp1 and mrp2 genes code for MRP1 and MRP2 proteins, respectively. In this study, the physiological modulation of the level of transcript for these genes during rat ontogeny in the liver, kidney, lung, brain and heart was analyzed by reverse transcription‐polymerase chain reaction. An increasing level of transcript during ontogeny was demonstrated for mdr1a and mdr1b in all tissues considered, as well as for mrp2 , which was detected only in the liver and kidney. In contrast, mrp1 transcript, present in all tissues, did not show any modulation. The maximum level of expression was reached in adult animals and a significant decrease was demonstrated in aging rats. Western blot analysis with C219 and M 2 III-6 monoclonal antibodies confirmed this different pattern of expression during ontogeny in the liver. The physiological regulation of cytochrome P450 3A2 was also considered: in the rat liver, an increase in the level of transcript during ontogeny, with a maximum in 60-day-old rats and a decrease in 8-month-old rats, was evident. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|