title: Reduction of MDR3 mRNA levels by forskolin in Chang liver cells.
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.
  
  
  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.
authors.affiliation: Department of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Ikuo
authors.initials: I
authors.lastname: Machida
authors.forename: Hisao
authors.initials: H
authors.lastname: Hayashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Wakusawa
mesh_terms: 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
chemical_list: 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