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

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Transcriptional Control of Intestinal Cytochrome P-4503A by 1α,25-Dihydroxy Vitamin D3

Kenneth E. Thummel, Cynthia Brimer, Kazuto Yasuda, Jaideep Thottassery, Tauri Senn, Yvonne Lin, Hitoshi Ishizuka, Evan Kharasch, John Schuetz and Erin Schuetz
Molecular Pharmacology December 2001, 60 (6) 1399-1406; DOI: https://doi.org/10.1124/mol.60.6.1399
Kenneth E. Thummel
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cynthia Brimer
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuto Yasuda
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jaideep Thottassery
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tauri Senn
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yvonne Lin
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hitoshi Ishizuka
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Evan Kharasch
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John Schuetz
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erin Schuetz
1Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and 2Department of Anesthesiology (E.K.), University of Washington, Seattle, Washington; and 3Department of Pharmaceutical Sciences (C.B., K.Y., J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis, Tennessee
  • 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

It was previously shown that CYP3A4 is induced in the human intestinal Caco-2 cell model by treatment with 1α,25-dihydroxy vitamin D3 (1,25-D3). We demonstrate the vitamin D analog, 19-nor-1α,25-dihydroxy vitamin D2, is also an effective inducer of CYP3A4 in Caco-2 cells, but with half the potency of 1,25-D3. We report that treatment of LS180 cells, a human intestinal cell line, with 1 to 10 nM 1,25-D3 dose dependently increased CYP3A4 protein and CYP3A4 mRNA expression.CYP3A4- and CYP3A23-promoter-Luciferase reporter constructs transiently transfected into LS180 cells were transcriptionally activated in a dose-dependent manner by 1,25-D3, whereas mutation of the nuclear hormone receptor binding motif (ER6) in the CYP3A4 promoter abrogated 1,25-D3 activation of CYP3A4. Although theCYP3A4 ER6 promoter element has been shown to bind the pregnane X receptor (PXR), this receptor does not mediate 1,25-D3 induction of CYP3A4 because a) PXR is not expressed in Caco-2 cells; b) PXR mRNA expression is not induced by 1,25-D3 treatment of LS180 cells; and c) the ligand binding domain of human PXR was not activated by 1,25-D3. 1,25-D3 uses the vitamin D receptor to induce CYP3A4 because a) the vitamin D receptor (VDR)-retinoid X receptor (RXR) heterodimer binds specifically to the CYP3A4 ER6; b) selective mutation of the CYP3A4 ER6 disrupted the binding of VDR-RXR; and c) reporter constructs containing only three copies of the CYP3A4 ER6 linked to a TK-CAT reporter were activated by 1,25-D3 only in cells cotransfected with a human VDR expression plasmid. These data support the hypothesis that 1,25-D3 and VDR induce expression of intestinal CYP3A by binding of the activated VDR-RXR heterodimer to theCYP3A PXR response element and promoting gene transcription.

  • 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

Molecular Pharmacology: 60 (6)
Molecular Pharmacology
Vol. 60, Issue 6
1 Dec 2001
  • 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 Molecular Pharmacology 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.
Transcriptional Control of Intestinal Cytochrome P-4503A by 1α,25-Dihydroxy Vitamin D3
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
Citation Tools
Research ArticleArticle

Transcriptional Control of Intestinal Cytochrome P-4503A by 1α,25-Dihydroxy Vitamin D3

Kenneth E. Thummel, Cynthia Brimer, Kazuto Yasuda, Jaideep Thottassery, Tauri Senn, Yvonne Lin, Hitoshi Ishizuka, Evan Kharasch, John Schuetz and Erin Schuetz
Molecular Pharmacology December 1, 2001, 60 (6) 1399-1406; DOI: https://doi.org/10.1124/mol.60.6.1399

Citation Manager Formats

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

Transcriptional Control of Intestinal Cytochrome P-4503A by 1α,25-Dihydroxy Vitamin D3

Kenneth E. Thummel, Cynthia Brimer, Kazuto Yasuda, Jaideep Thottassery, Tauri Senn, Yvonne Lin, Hitoshi Ishizuka, Evan Kharasch, John Schuetz and Erin Schuetz
Molecular Pharmacology December 1, 2001, 60 (6) 1399-1406; DOI: https://doi.org/10.1124/mol.60.6.1399
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
    • Experimental Procedures
    • Results
    • Discussion
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • BODIPY-cyclopamine Binding to Nluc-SMO
  • Operational Models for Receptors with Multiple Agonist Sites
  • Characterization and optimization of the novel TRPM2 antagonist tatM2NX
Show more Article

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 Molecular Pharmacology
  • 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
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

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