Effect of Glucocorticoid Receptor Ligand Dexamethasone on the Expression of Organic Cation Transporter in Rat Liver

• MAEDA Tomoji

  Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Tokyo University of Science

• YOTSUMOTO Takafumi

  Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Tokyo University of Science

• OYABU Masanobu

  Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Tokyo University of Science

• TAMAI Ikumi

  Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Tokyo University of Science

Abstract

  Since rat organic cation transporter 1 (Oct1, Slc22a1) is expressed mainly in the liver and mediates drug transport, its activity may determine the hepatic handling of cationic drugs. Here, we studied the regulation mechanism of the expression of rat Oct1, focusing on the nuclear receptors. Various nuclear receptors are considered to regulate expressions of many genes for membrane transporters and enzymes that are involved in the drug absorption and disposition. Previously, we demonstrated that some ligands of nuclear receptors affected the transcriptional regulation of rat Oct1 when examined in the primary cultured rat hepatocytes. In the present study, dexamethasone, a ligand of glucocorticoid receptor, down-regulated the expression of rat Oct1. In addition, the transport activity of rat Oct1, evaluated by the uptake of substrates of rat Oct1, was decreased by treatment of dexamethasone in comparison with untreated rat hepatocytes, showing a good agreement with the change in mRNA level. In conclusion, these observations suggested that the expression of rat Oct1 gene and the apparent organic cation uptake activity of rat hepatocytes are down-regulated by dexamethasone presumably via a glucocorticoid receptor.<br>

Journal

• Drug Metabolism and Pharmacokinetics

  Drug Metabolism and Pharmacokinetics 23 (1), 67-72, 2008

  The Japanese Society for the Study of Xenobiotics

Keywords

• organic cation transporter 1 (Oct1)
• dexamethasone
• glucocorticoid receptor
• nuclear receptors
• rat liver

Details

• CRID: 1390001205178458368
• NII Article ID: 10024187802
• NII Book ID: AA1162652X
• DOI: 10.2133/dmpk.23.67
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301592?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301592?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2008175547
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed