Abstract
Background:
MDR3 is a phospholipid translocator and a putative transporter of several drugs in the canalicular membrane of hepatocytes. To clarify the regulatory system for the expression of MDR3 mRNA in comparison with MDR1 mRNA, we examined the effect of cyclic AMP using forskolin.
Materials and methods:
Chang liver cells were treated with forskolin, and then MDR3 and MDR1 mRNA levels were examined by RT-PCR and the MDR3 protein level was examined by Western blotting.
Results:
The MDR3 mRNA level decreased while the MDR1 mRNA level increased, and the effects of forskolin were inhibited by a protein kinase A inhibitor, H-89. The MDR3 protein level was not changed by forskolin. However, forskolin decreased the induction of MDR3 mRNA expression by doxorubicin.
Conclusion:
The level of MDR3 mRNA was negatively-regulated by a cyclic AMP- and protein kinase A-dependent system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / biosynthesis*
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ATP Binding Cassette Transporter, Subfamily B / genetics
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ATP-Binding Cassette Transporters / biosynthesis*
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ATP-Binding Cassette Transporters / genetics
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Cells, Cultured
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Colforsin / pharmacology*
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Down-Regulation / drug effects
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Doxorubicin / pharmacology
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Enzyme Inhibitors / pharmacology
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Humans
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Isoquinolines / pharmacology
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Liver / cytology
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Liver / drug effects*
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Liver / enzymology
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Liver / metabolism
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism*
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Sulfonamides*
Substances
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ATP Binding Cassette Transporter, Subfamily B
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ATP-Binding Cassette Transporters
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Enzyme Inhibitors
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Isoquinolines
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RNA, Messenger
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Sulfonamides
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Colforsin
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Doxorubicin
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multidrug resistance protein 3
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Cyclic AMP-Dependent Protein Kinases
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide