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
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
  • My Cart
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Abstract

Ah receptor in mice genetically "nonresponsive" for cytochrome P4501A1 induction: cytosolic Ah receptor, transformation to the nuclear binding state, and induction of aryl hydrocarbon hydroxylase by halogenated and nonhalogenated aromatic hydrocarbons in embryonic tissues and cells.

P A Harper, C L Golas and A B Okey
Molecular Pharmacology November 1991, 40 (5) 818-826;
P A Harper
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C L Golas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A B Okey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The aromatic hydrocarbon (Ah) receptor mediates induction of cytochrome P4501A1 and associated aryl hydrocarbon hydroxylase (AHH) activity in tissues or cells exposed to polycyclic aromatic hydrocarbons. Strains of mice designated "nonresponsive" do not show increased hepatic AHH activity when exposed in vivo to nonhalogenated aromatic hydrocarbons such as 3-methylcholanthrene, benz[a]anthracene (BA), or benzo[a]pyrene and have reduced sensitivity to halogenated inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recently, with a modified assay, we detected Ah receptor in hepatic cytosols from adult nonresponsive mice [Mol. Pharmacol. 35:823-830 (1989)]; the receptor was present in reduced amount, and the apparent affinity for TCDD was lower than in hepatic cytosol from responsive C57BL/6J mice. Using the same assay procedure, we now report detection of Ah receptor in cytosols prepared from embryonic tissue and from cultured embryo cells of both responsive (C57BL/6J) and nonresponsive mice (DBA/2J, AKR/J, and SWR/J). Cytosolic receptor in embryonic cells from nonresponsive as well as responsive strains was detectable both with [3H]TCDD and with [3H]3-methylcholanthrene. In addition, the receptor-ligand complex could be extracted from nuclei of embryo cells exposed to [3H]TCDD in culture. AHH activity was induced in embryo cell cultures incubated with either TCDD or BA. The EC50 values for AHH induction were virtually identical in cell cultures from nonresponsive (DBA/2J) and responsive (C57BL/6J) strains, using either TCDD or BA as the inducer. Moreover, the affinity with which [3H]TCDD bound to cytosolic Ah receptor was much more similar in cytosols from cell cultures from the two strains than in cytosols prepared from adult liver. Thus, embryonic cell cultures differ in at least three respects from the adult liver, as follows: (i) Ah receptor can be detected with [3H]3-methylcholanthrene in embryonic cell cytosols but not in cytosols from adult liver; (ii) the degree of difference between nonresponsive and responsive strains in the affinity with which [3H]TCDD binds to receptor is only about 2-fold in cytosol from embryonic cells, whereas it is almost 10-fold in adult liver; and (iii) induction of AHH activity (by either TCDD or by the nonhalogenated inducer BA) shows no significant difference between strains in embryonic cell culture, whereas there is at least a 15-fold difference in responsiveness between C57BL/6J and DBA/2J mice in adult liver in vivo. The mechanistic reason for the diminished degree of difference between responsive and nonresponsive mice during embryonic cell culture (compared with adult tissues) is not yet known.

MolPharm 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

Molecular Pharmacology
Vol. 40, Issue 5
1 Nov 1991
  • Table of Contents
  • Table of Contents (PDF)
  • 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 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.
Ah receptor in mice genetically "nonresponsive" for cytochrome P4501A1 induction: cytosolic Ah receptor, transformation to the nuclear binding state, and induction of aryl hydrocarbon hydroxylase by halogenated and nonhalogenated aromatic hydrocarbons in…
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Abstract

Ah receptor in mice genetically "nonresponsive" for cytochrome P4501A1 induction: cytosolic Ah receptor, transformation to the nuclear binding state, and induction of aryl hydrocarbon hydroxylase by halogenated and nonhalogenated aromatic hydrocarbons in embryonic tissues and cells.

P A Harper, C L Golas and A B Okey
Molecular Pharmacology November 1, 1991, 40 (5) 818-826;

Citation Manager Formats

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

Share
Abstract

Ah receptor in mice genetically "nonresponsive" for cytochrome P4501A1 induction: cytosolic Ah receptor, transformation to the nuclear binding state, and induction of aryl hydrocarbon hydroxylase by halogenated and nonhalogenated aromatic hydrocarbons in embryonic tissues and cells.

P A Harper, C L Golas and A B Okey
Molecular Pharmacology November 1, 1991, 40 (5) 818-826;
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
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

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 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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics