Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • 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
  • My Cart

Search

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

Advanced Search

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

Species Differences in the Transport Activity for Organic Anions across the Bile Canalicular Membrane

Hitoshi Ishizuka, Kumiko Konno, Tetsuo Shiina, Hideo Naganuma, Kenji Nishimura, Kousei Ito, Hiroshi Suzuki and Yuichi Sugiyama
Journal of Pharmacology and Experimental Therapeutics September 1999, 290 (3) 1324-1330;
Hitoshi Ishizuka
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kumiko Konno
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tetsuo Shiina
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hideo Naganuma
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenji Nishimura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kousei Ito
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Suzuki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuichi Sugiyama
  • 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

Species differences in the transport activity mediated by canalicular multispecific organic anion transporter (cMOAT) were examined using temocaprilat, an angiotensin-converting enzyme inhibitor whose biliary excretion is mediated predominantly by cMOAT, and 2,4-dinitrophenyl-S-glutathione, a typical substrate for cMOAT, in a series of in vivo and in vitro experiments. Temocaprilat was infused to examine the biliary excretion rate at steady-state. The in vivo transport clearance values across the bile canalicular membrane, defined as the biliary excretion rate divided by the hepatic unbound concentrations, were 9.8, 39.2, 9.2, 1.1, and 0.8 ml/min/kg for mouse, rat, guinea pig, rabbit, and dog, respectively. TheKm and Vmaxvalues for ATP-dependent uptake of 2,4-dinitrophenyl-S-glutathione into canalicular membrane vesicles were 15.0, 29.6, 16.1, 55.8, and 30.0 μM and 0.38, 1.90, 0.15, 0.47, and 0.23 nmol/min/mg protein, yielding the in vitro transport clearance across the bile canalicular membrane (Vmax/Km) of 25.5, 64.2, 9.4, 8.4, and 7.7 for mouse, rat, guinea pig, rabbit, and dog, respectively. A close in vivo and in vitro correlation was observed among animal species for the transport clearance across the bile canalicular membrane. These results suggest that the uptake experiments with canalicular membrane vesicles can be used to quantitatively predict in vivo excretion across the bile canalicular membrane.

Footnotes

  • Send reprint requests to: Dr. Hitoshi Ishizuka, Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. E-mail:ishizu{at}shina.sankyo.co.jp

  • ↵1 This work was supported in part by a grant-in-aid for Scientific Research on Priority Areas “ABC proteins” (10044243) from the Ministry of Education, Science and Culture of Japan and the Core Research for Evolutional Sciences and Technology of the Japan Sciences and Technology Corporation.

  • Abbreviations:
    CMV
    canalicular membrane vesicles
    cMOAT
    canalicular multispecific organic anion transporter
    SD
    Sprague-Dawley
    EHBR
    Eisai hyperbilirubinemic rat
    DNP-SG
    2,4-dinitrophenyl-S-glutathione
    ALP
    alkaline phosphatase
    LAP
    leucine aminopeptidase
    γ-GTPase
    γ-glutamyl transpeptidase
    GST
    glutathione S-transferase
    CLbile(plasma)
    biliary excretion clearance defined by plasma concentration
    CLbile(liver)
    biliary excretion clearance defined by the liver concentration
    CLbile(u,liver)
    biliary excretion clearance defined by the liver unbound concentration
    Cplasma
    plasma concentration
    Cliver
    liver concentration
    Cu,liver
    liver unbound concentration
    fu,plasma
    the plasma unbound fraction
    fu,liver
    the liver unbound fraction
    MRP
    multidrug resistance-associated protein
    BSEP
    bile salt export pump
    • Received November 10, 1998.
    • Accepted May 21, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 290 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 290, Issue 3
1 Sep 1999
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics 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.
Species Differences in the Transport Activity for Organic Anions across the Bile Canalicular Membrane
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Species Differences in the Transport Activity for Organic Anions across the Bile Canalicular Membrane

Hitoshi Ishizuka, Kumiko Konno, Tetsuo Shiina, Hideo Naganuma, Kenji Nishimura, Kousei Ito, Hiroshi Suzuki and Yuichi Sugiyama
Journal of Pharmacology and Experimental Therapeutics September 1, 1999, 290 (3) 1324-1330;

Citation Manager Formats

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

Share
Research ArticleArticle

Species Differences in the Transport Activity for Organic Anions across the Bile Canalicular Membrane

Hitoshi Ishizuka, Kumiko Konno, Tetsuo Shiina, Hideo Naganuma, Kenji Nishimura, Kousei Ito, Hiroshi Suzuki and Yuichi Sugiyama
Journal of Pharmacology and Experimental Therapeutics September 1, 1999, 290 (3) 1324-1330;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PST3093 Stimulates SERCA2a and Improves Cardiac Function
  • CRV431 Decreases Liver Fibrosis and Tumor Development
  • Pharmacological Characterization of Nicotine-Induced Seizures in Mice
Show more Article

Similar Articles

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

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics