Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Effect of Pregnane X Receptor Ligand on Pharmacokinetics of Substrates of Organic Cation Transporter Oct1 in Rats

Tomoji Maeda, Masanobu Oyabu, Takafumi Yotsumoto, Ryunosuke Higashi, Kiyoshi Nagata, Yasushi Yamazoe and Ikumi Tamai
Drug Metabolism and Disposition September 2007, 35 (9) 1580-1586; DOI: https://doi.org/10.1124/dmd.107.015842
Tomoji Maeda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masanobu Oyabu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takafumi Yotsumoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryunosuke Higashi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kiyoshi Nagata
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yasushi Yamazoe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ikumi Tamai
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Because 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 Oct1, focusing on the nuclear receptors. In vitro studies using cultured hepatocytes indicated that expression of Oct1 was up-regulated by treatment with pregnenolone-16α-carbonitrile (PCN) and by overexpression of rat pregnane X receptor (PXR). In addition, isolated rat hepatocytes exhibited an increase of 1-methyl-4-phenylpyridinium (MPP+) uptake on treatment with PCN. When rats were subcutaneously administered PCN, an increase of biliary excretion clearance and distribution volume was observed for drugs such as MPP+, metformin, and tetraethylammonium, although the effects on pharmacokinetic parameters were variable among the tested drugs. In addition, the expression of Oct2 in kidney was increased by treatment with PCN. Thus, PXR ligands appear to regulate the expression of organic cation transporters in rats and thereby to influence the pharmacokinetic properties of cationic drugs. Because PXR ligands include various clinically used drugs, alterations of hepatic drug handling may arise from interactions between cationic drugs that are substrates of Oct1 and ligands of PXR.

Footnotes

  • This study was supported in part by a Grant in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

  • doi:10.1124/dmd.107.015842.

  • ABBREVIATIONS: OCT (Oct), organic cation transporter; AUC, area under the plasma concentration-time curve; CLbile, biliary excretion clearance; Vd, distribution volume; DMEM, Dulbecco's modified Eagle's medium; DR, direct repeat; ER, everted repeat; FBS, fetal bovine serum; G3PDH, glyceraldehyde-3-phosphate dehydrogenase; HNF4α, hepatocyte nuclear factor-4α; MPP+, 1-methyl-4-phenylpyridinium; Ntcp, sodium/taurocholate cotransporter; PBS, phosphate-buffered saline; PCN, pregnenolone-16α-carbonitrile; PPAR, peroxisome proliferator-activated receptor; PXR, pregnane X receptor; PXRE, PXR response element; RT-PCR, reverse transcription polymerase chain reaction; TCA, taurocholic acid; TEA, tetraethylammonium.

    • Received March 16, 2007.
    • Accepted June 5, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

Log in using your username and password

Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 35 (9)
Drug Metabolism and Disposition
Vol. 35, Issue 9
1 Sep 2007
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Effect of Pregnane X Receptor Ligand on Pharmacokinetics of Substrates of Organic Cation Transporter Oct1 in Rats
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
Citation Tools
Research ArticleArticle

Effect of Pregnane X Receptor Ligand on Pharmacokinetics of Substrates of Organic Cation Transporter Oct1 in Rats

Tomoji Maeda, Masanobu Oyabu, Takafumi Yotsumoto, Ryunosuke Higashi, Kiyoshi Nagata, Yasushi Yamazoe and Ikumi Tamai
Drug Metabolism and Disposition September 1, 2007, 35 (9) 1580-1586; DOI: https://doi.org/10.1124/dmd.107.015842

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

Effect of Pregnane X Receptor Ligand on Pharmacokinetics of Substrates of Organic Cation Transporter Oct1 in Rats

Tomoji Maeda, Masanobu Oyabu, Takafumi Yotsumoto, Ryunosuke Higashi, Kiyoshi Nagata, Yasushi Yamazoe and Ikumi Tamai
Drug Metabolism and Disposition September 1, 2007, 35 (9) 1580-1586; DOI: https://doi.org/10.1124/dmd.107.015842
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Abundant expression of OCT2, MATE1, OAT1, OAT3, PEPT2, BCRP, MDR1 and xCT transporters in blood-arachnoid barrier of pig, and polarized localizations at CSF- and blood-facing plasma membranes
  • Pharmacokinetics of Organic Cation Transporter 1 (OCT1) Substrates in Oct1/2 Knockout Mice and Species Difference in Hepatic OCT1-mediated Uptake
  • Human Cytochrome P450 1A1 Adapts Active Site for Atypical Nonplanar Substrate
Show more Articles

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2019 by the American Society for Pharmacology and Experimental Therapeutics