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
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
    • 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 dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

VERAPAMIL: METABOLISM IN CULTURES OF PRIMARY HUMAN CORONARY ARTERIAL ENDOTHELIAL CELLS

Jürgen Borlak, Markus Walles, Karsten Levsen and Thomas Thum
Drug Metabolism and Disposition July 2003, 31 (7) 888-891; DOI: https://doi.org/10.1124/dmd.31.7.888
Jürgen Borlak
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Markus Walles
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karsten Levsen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Thum
  • 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

Endothelium is a metabolically active secretory tissue and an important barrier for metabolic products. Little is known about its contribution to drug oxidation. We investigated the gene and protein expression and enzyme activity of major cytochrome P450 monooxygenases in cultures of primary human coronary endothelial cells and studied its ability to metabolize verapamil, a commonly and widely prescribed calcium antagonist. Of the total 18 P450 monooxygenases investigated, transcripts for CYP1A1, CYP2A6/7, CYP2A13, CYP2B6/7, CYP2C8, CYP2E1, and CYP2J2 were expressed, albeit at different levels. Furthermore, metabolism of verapamil proceeded predominantly via N-desmethylation and/or N-desalkylation, i.e., production of D-617 [2-(3,4-dimethoxyphenyl)-5-amino-2-isopropylvaleronitrile], D-620 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile], and norverapamil; but additional metabolites are the O-demethylated products, D-702 [2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] and D-703 [O-demethylverapamil; 5-N-(3,4-dimethoxyphenethyl)methylamino-2-(3′-methoxy-4′-hydroxyphenyl)-2-isopropylvaleronitrile]. We show endothelium to express an array of monooxygenases, and in view of its large body distribution, endothelium should be considered in the biotransformation of drugs, particularly when tissue-specific metabolism and/or metabolic inactivation are being investigated.

Footnotes

  • ↵1 Abbreviations used are: D-617, 2-(3,4-dimethoxyphenyl)-5-amino-2-isopropylvaleronitrile; D-620, 2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile; D-702, 2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile; PECAM-1, platelet endothelial cell adhesion molecule-1; PCR, polymerase chain reaction; TBS, Tris-buffered saline; D-703, O-demethylverapamil [5-N-(3,4-dimethoxyphenethyl)methylamino-2-(3′-methoxy-4′-hydroxyphenyl)-2-isopropylvaleronitrile]; P450, cytochrome P450; LC/MS, liquid chromatography-mass spectrometry.

    • Received October 28, 2002.
    • Accepted March 20, 2003.
  • 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: 31 (7)
Drug Metabolism and Disposition
Vol. 31, Issue 7
1 Jul 2003
  • 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.
VERAPAMIL: METABOLISM IN CULTURES OF PRIMARY HUMAN CORONARY ARTERIAL ENDOTHELIAL CELLS
(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

VERAPAMIL: METABOLISM IN CULTURES OF PRIMARY HUMAN CORONARY ARTERIAL ENDOTHELIAL CELLS

Jürgen Borlak, Markus Walles, Karsten Levsen and Thomas Thum
Drug Metabolism and Disposition July 1, 2003, 31 (7) 888-891; DOI: https://doi.org/10.1124/dmd.31.7.888

Citation Manager Formats

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

Share
Research ArticleArticle

VERAPAMIL: METABOLISM IN CULTURES OF PRIMARY HUMAN CORONARY ARTERIAL ENDOTHELIAL CELLS

Jürgen Borlak, Markus Walles, Karsten Levsen and Thomas Thum
Drug Metabolism and Disposition July 1, 2003, 31 (7) 888-891; DOI: https://doi.org/10.1124/dmd.31.7.888
del.icio.us logo Digg logo Reddit logo Twitter 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

  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
Show more Articles

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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics