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
Research ArticleArticle

Steroid Inhibition of Rat Neuronal Nicotinic α4β2 Receptors Expressed in HEK 293 Cells

Ken Paradiso, Kimberley Sabey, Alex S. Evers, Charles F. Zorumski, Douglas F. Covey and Joe Henry Steinbach
Molecular Pharmacology August 2000, 58 (2) 341-351; DOI: https://doi.org/10.1124/mol.58.2.341
Ken Paradiso
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kimberley Sabey
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alex S. Evers
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Charles F. Zorumski
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas F. Covey
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joe Henry Steinbach
Departments of 1 2 3
  • 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

Steroids, in addition to regulating gene expression, directly affect a variety of ion channels. We examined the action of steroids on human embryonic kidney 293 cells stably transfected to express rat α4β2 neuronal nicotinic receptors. Each steroid that was tested inhibited acetylcholine responses from these receptors, with slow kinetics requiring seconds for block to develop and recover. The action of one steroid [3α,5α,17β-3-hydroxyandrostane-17-carbonitrile (ACN)] was studied in detail. Block showed enantioselectivity, with an IC50 value of 1.5 μM for ACN and 4.5 μM for the enantiomer. Inhibition curves had Hill slopes larger than 1, indicating more than one binding site per receptor. Block did not require intracellular compounds containing high-energy phosphate bonds and was not affected by analogs of GTP, suggesting that the mechanism does not require the activation of second messengers. Block did not appear to be strongly selective between open and closed channel states or to involve changes in desensitization. A comparison of different steroids showed that a β-orientation of groups at the 17 position produced more block than α-orientated diastereomers. The stereochemistry at the 3 and 5 positions was less influential for block of α4β2 nicotinic receptors, despite its importance for potentiation of γ-aminobutyric acidA receptors. The ability of steroids to block neuronal nicotinic receptors correlated with their ability to produce anesthesia in Xenopus tadpoles, but the concentrations required for inhibition are generally greater. Similarly, the concentrations of endogenous neurosteroids required to inhibit receptors are larger than estimates of brain concentrations.

Footnotes

    • Received February 23, 2000.
    • Accepted May 11, 2000.
  • Send reprint requests to: Dr. Joe Henry Steinbach, Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110. E-mail:jhs{at}morpheus.wustl.edu

  • ↵1 This work was supported by National Institutes of Health Grants P01-GM47969 (J.H.S., D.F.C., A.E., C.Z.) and R01-NS22356 (J.H.S.) J.H.S. is the Russell and Mary Shelden Professor of Anesthesiology.

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

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: 58 (2)
Molecular Pharmacology
Vol. 58, Issue 2
1 Aug 2000
  • 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.
Steroid Inhibition of Rat Neuronal Nicotinic α4β2 Receptors Expressed in HEK 293 Cells
(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
Research ArticleArticle

Steroid Inhibition of Rat Neuronal Nicotinic α4β2 Receptors Expressed in HEK 293 Cells

Ken Paradiso, Kimberley Sabey, Alex S. Evers, Charles F. Zorumski, Douglas F. Covey and Joe Henry Steinbach
Molecular Pharmacology August 1, 2000, 58 (2) 341-351; DOI: https://doi.org/10.1124/mol.58.2.341

Citation Manager Formats

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

Share
Research ArticleArticle

Steroid Inhibition of Rat Neuronal Nicotinic α4β2 Receptors Expressed in HEK 293 Cells

Ken Paradiso, Kimberley Sabey, Alex S. Evers, Charles F. Zorumski, Douglas F. Covey and Joe Henry Steinbach
Molecular Pharmacology August 1, 2000, 58 (2) 341-351; DOI: https://doi.org/10.1124/mol.58.2.341
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
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • The binding site for KCI807 in the androgen receptor
  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
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 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