Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
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
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Carrier-Mediated Active Transport of a Novel Thromboxane A2 Receptor Antagonist [2-(4-Chlorophenylsulfonylaminomethyl)indan-5-yl]acetate (Z-335) into Rat Liver

Yoshihiro Kawabata, Shigeru Furuta, Yutaka Shinozaki, Tadashi Kurimoto and Ryuichiro Nishigaki
Drug Metabolism and Disposition May 2002, 30 (5) 498-504; DOI: https://doi.org/10.1124/dmd.30.5.498
Yoshihiro Kawabata
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shigeru Furuta
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yutaka Shinozaki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tadashi Kurimoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryuichiro Nishigaki
  • 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

To elucidate the transport system by which [2-(4-chlorophenylsulfonylaminomethyl)indan-5-yl]acetate (Z-335) is taken up into the liver, we investigated the uptake characteristics of Z-335 in isolated rat hepatocytes. In addition, we estimated the hepatic uptake of Z-335 in intact rats under steady-state conditions and compared it with the in vitro uptake clearance. Uptake of Z-335 is highly concentrative (cell-to-medium concentration ratios were 21.2 at 0.5 min and 71.7 at 5 min), temperature-dependent, and sensitive to metabolic inhibitors, indicating that uptake is mediated by energy-dependent uphill transport. In the presence of metabolic inhibitors [carbonyl cyanidep-trifluoromethoxyphenylhydrazone and rotenone], uptake remained at 37 and 49% of the control value, respectively, suggesting that ATP-independent uptake contributes to the total uptake of Z-335. The concentration dependence of the initial uptake velocity indicated a two-component process, one saturable component, with aKm value of 45.6 μM and aVmax value of 4.1 nmol/min/mg of protein, and a nonspecific diffusion clearance, with aPdif value of 8.3 μl/min/mg of protein. The contribution of the carrier-mediated uptake to the total uptake in a linear range was estimated as 91%. The in vivo hepatic intrinsic clearance (CLint, app) was comparable with that in vitro uptake clearance (PSinflux) and indicated that the CLint, app of Z-335 at steady state is rate-limited by the uptake process. In conclusion, hepatic intrinsic clearance of Z-335 at steady state is rate-limited by the uptake process since Z-335 is efficiently taken up by an active transport mechanism, followed by metabolism or biliary excretion.

Footnotes

  • Abbreviations used are::
    Z-335
    [2-(4-chlorophenylsulfonylaminomethyl)indan-5-yl]acetate
    TXA2
    thromboxane A2
    SQ-29548
    1S-[1α,2β(5Z),3β,4α]-7-[3-[[2-[(phenylamino) carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid
    U-46619
    11,9 epoxymethano-prostaglandin H2
    oatp
    organic anion transporting polypeptide
    ID910096
    sodium [2-(4-chlorophenylsulfonylaminomethyl)indan-5-yl]ethylcarboxylate
    FCCP
    carbonyl cyanidep-trifluoromethoxyphenylhydrazone
    BSP
    bromosulfophthalein
    C/M ratio
    cell-to-medium concentration ratio
    PSinflux
    permeability-surface product
    CL
    clearance
    oat
    organic anion transporter
    • Received September 14, 2001.
    • Accepted January 18, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD 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

Drug Metabolism and Disposition: 30 (5)
Drug Metabolism and Disposition
Vol. 30, Issue 5
1 May 2002
  • 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 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.
Carrier-Mediated Active Transport of a Novel Thromboxane A2 Receptor Antagonist [2-(4-Chlorophenylsulfonylaminomethyl)indan-5-yl]acetate (Z-335) into Rat Liver
(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.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Carrier-Mediated Active Transport of a Novel Thromboxane A2 Receptor Antagonist [2-(4-Chlorophenylsulfonylaminomethyl)indan-5-yl]acetate (Z-335) into Rat Liver

Yoshihiro Kawabata, Shigeru Furuta, Yutaka Shinozaki, Tadashi Kurimoto and Ryuichiro Nishigaki
Drug Metabolism and Disposition May 1, 2002, 30 (5) 498-504; DOI: https://doi.org/10.1124/dmd.30.5.498

Citation Manager Formats

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

Carrier-Mediated Active Transport of a Novel Thromboxane A2 Receptor Antagonist [2-(4-Chlorophenylsulfonylaminomethyl)indan-5-yl]acetate (Z-335) into Rat Liver

Yoshihiro Kawabata, Shigeru Furuta, Yutaka Shinozaki, Tadashi Kurimoto and Ryuichiro Nishigaki
Drug Metabolism and Disposition May 1, 2002, 30 (5) 498-504; DOI: https://doi.org/10.1124/dmd.30.5.498
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

  • Retroconversion of PQ and Its N-Oxide Metabolites
  • Deoxycholate Oxidation Is Predictive of CYP3A Activity
  • REF vs RAF Prediction of Renal Clearance
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 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics