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

A Role of p75 in NGF-Mediated Down-Regulation of the A2A Adenosine Receptors in PC12 Cells

Zhongzhen Nie, Yun Mei, Renae L. Malek, Adriana Marcuzzi, Norman H. Lee and Vickram Ramkumar
Molecular Pharmacology November 1999, 56 (5) 947-954; DOI: https://doi.org/10.1124/mol.56.5.947
Zhongzhen Nie
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yun Mei
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Renae L. Malek
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adriana Marcuzzi
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Norman H. Lee
Departments of 1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vickram Ramkumar
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

Nerve growth factor (NGF) induces differentiation of the rat pheochromocytoma clone (PC12) by activating the high affinity receptor, p140trkA, linked to mitogen-activated protein kinase. While the physiological role of the low affinity NGF receptor (p75) has not been clearly defined, this receptor promotes activation of nuclear factor (NF) κB in Schwann cells. PC12 cells express the A2A adenosine receptor (AR), whose expression is significantly decreased by NGF treatment. In this study, we determined whether TrkA or p75 is involved in NGF-mediated regulation of A2AAR expression. NGF treatment decreased A2AAR in a time-dependent manner, with maximal effects observed by 1 day, and continued down-regulation of the receptor for up to 3 days in the presence of NGF. The decrease in A2AAR was associated with a more delayed decrease in the steady-state levels of the A2AAR mRNA. Down-regulation of the A2AAR at 1 day was mimicked by activators of NFκB, such as H2O2, and ceramide, and was attenuated by the inhibitor pyrrolidine dithiocarbamate or following transient transfection of PC12 cells with a dominant negative IκBα mutant. Moreover, NGF stimulated nuclear accumulation of p65 subunits of NFκB (but not p50 subunits) in PC12 cells, as determined by electrophoretic mobility shift assays and by Western blotting. In contrast, inhibition of TrkA by AG879 or of TrkA-dependent mitogen-activated protein kinase mitogen-activated protein kinase kinase with PD98059 blocked PC12 cell differentiation without affecting A2AAR down-regulation, suggesting dissociation between these two phenomena. Taken together, these data provide strong support for the involvement of the p75/NFκB pathway in NGF-mediated down-regulation of A2AAR in PC12 cells.

Footnotes

    • Received March 1, 1999.
    • Accepted August 6, 1999.
  • Send reprint requests to: Dr. Vickram Ramkumar, Department of Pharmacology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629. E-mail: vramkumar{at}siumed.edu

  • This work was supported in part by National Institutes of Health Grants NS35231 (to N.H.L.) and HL56316 (to V.R.).

  • 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: 56 (5)
Molecular Pharmacology
Vol. 56, Issue 5
1 Nov 1999
  • 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.
A Role of p75 in NGF-Mediated Down-Regulation of the A2A Adenosine Receptors in PC12 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

A Role of p75 in NGF-Mediated Down-Regulation of the A2A Adenosine Receptors in PC12 Cells

Zhongzhen Nie, Yun Mei, Renae L. Malek, Adriana Marcuzzi, Norman H. Lee and Vickram Ramkumar
Molecular Pharmacology November 1, 1999, 56 (5) 947-954; DOI: https://doi.org/10.1124/mol.56.5.947

Citation Manager Formats

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

Share
Research ArticleArticle

A Role of p75 in NGF-Mediated Down-Regulation of the A2A Adenosine Receptors in PC12 Cells

Zhongzhen Nie, Yun Mei, Renae L. Malek, Adriana Marcuzzi, Norman H. Lee and Vickram Ramkumar
Molecular Pharmacology November 1, 1999, 56 (5) 947-954; DOI: https://doi.org/10.1124/mol.56.5.947
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results and Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Analgesic Effects and Mechanisms of Licochalcones
  • Induced Fit Ligand Binding to CYP3A4
  • Englerin A Inhibits T-Type Channels
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