Reduction of MDR3 mRNA levels by forskolin in Chang liver cells.
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.


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.


CONCLUSIONS
The level of MDR3 mRNA was negatively-regulated by a cyclic AMP- and protein kinase A-dependent system.
Suzuki
Satoshi
S
Department of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan.
Machida
Ikuo
I
Hayashi
Hisao
H
Wakusawa
Shinya
S
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis* / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D012333:RNA, Messenger; D013449:Sulfonamides; D005576:Colforsin; D004317:Doxorubicin; C095122:multidrug resistance protein 3; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide