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

Cell-Type Specific Effects of Endocytosis Inhibitors on 5-Hydroxytryptamine2A Receptor Desensitization and Resensitization Reveal an Arrestin-, GRK2-, and GRK5-Independent Mode of Regulation in Human Embryonic Kidney 293 Cells

John A. Gray, Douglas J. Sheffler, Anushree Bhatnagar, Jason A. Woods, Sandra J. Hufeisen, Jeffrey L. Benovic and Bryan L. Roth
Molecular Pharmacology November 2001, 60 (5) 1020-1030; DOI: https://doi.org/10.1124/mol.60.5.1020
John A. Gray
Departments of 1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas J. Sheffler
Departments of 1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anushree Bhatnagar
Departments of 1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason A. Woods
Departments of 1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sandra J. Hufeisen
Departments of 1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeffrey L. Benovic
Departments of 1 2 3 4
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bryan L. Roth
Departments of 1 2 3 4
  • 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

The effect of endocytosis inhibitors on 5-hydroxytryptamine2A (5-HT2A) receptor desensitization and resensitization was examined in transiently transfected human embryonic kidney (HEK) 293 cells and in C6 glioma cells that endogenously express 5-HT2A receptors. In HEK-293 cells, 5-HT2A receptor desensitization was unaffected by cotransfection with a dominant-negative mutant of dynamin (DynK44A), a truncation mutant of arrestin-2 [Arr2(319–418)], or by two well-characterized chemical inhibitors of endocytosis: concanavalin A (conA) and phenylarsine oxide (PAO). In contrast, β2-adrenergic receptor desensitization was significantly potentiated by each of these treatments in HEK-293 cells. In C6 glioma cells, however, DynK44A, Arr2(319–418), conA, and PAO each resulted in the potentiation of 5-HT2A and β-adrenergic receptor desensitization. The cell-type-specific effect of Arr2(319–418) on 5-HT2Areceptor desensitization was not related to the level of GRK2 or GRK5 expression. Interestingly, although β2-adrenergic receptor resensitization was potently blocked by cotransfection with DynK44A, 5-HT2A receptor resensitization was enhanced, suggesting the existence of a novel cell-surface mechanism for 5-HT2Areceptor resensitization in HEK-293 cells. In addition, Arr2(319–418) had no effect on 5-HT2A receptor resensitization in HEK-293 cells, although it attenuated the resensitization of the β2-adrenergic receptor. However, in C6 glioma cells, both DynK44A and Arr2(319–418) significantly reduced 5-HT2A receptor resensitization. Taken together, these results provide the first convincing evidence of cell-type-specific roles for endocytosis inhibitors in regulating GPCR activity. Additionally, these results imply that novel GRK and arrestin-independent mechanisms of 5-HT2A receptor desensitization and resensitization exist in HEK-293 cells.

  • 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: 60 (5)
Molecular Pharmacology
Vol. 60, Issue 5
1 Nov 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.
Cell-Type Specific Effects of Endocytosis Inhibitors on 5-Hydroxytryptamine2A Receptor Desensitization and Resensitization Reveal an Arrestin-, GRK2-, and GRK5-Independent Mode of Regulation in Human Embryonic Kidney 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

Cell-Type Specific Effects of Endocytosis Inhibitors on 5-Hydroxytryptamine2A Receptor Desensitization and Resensitization Reveal an Arrestin-, GRK2-, and GRK5-Independent Mode of Regulation in Human Embryonic Kidney 293 Cells

John A. Gray, Douglas J. Sheffler, Anushree Bhatnagar, Jason A. Woods, Sandra J. Hufeisen, Jeffrey L. Benovic and Bryan L. Roth
Molecular Pharmacology November 1, 2001, 60 (5) 1020-1030; DOI: https://doi.org/10.1124/mol.60.5.1020

Citation Manager Formats

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

Share
Research ArticleArticle

Cell-Type Specific Effects of Endocytosis Inhibitors on 5-Hydroxytryptamine2A Receptor Desensitization and Resensitization Reveal an Arrestin-, GRK2-, and GRK5-Independent Mode of Regulation in Human Embryonic Kidney 293 Cells

John A. Gray, Douglas J. Sheffler, Anushree Bhatnagar, Jason A. Woods, Sandra J. Hufeisen, Jeffrey L. Benovic and Bryan L. Roth
Molecular Pharmacology November 1, 2001, 60 (5) 1020-1030; DOI: https://doi.org/10.1124/mol.60.5.1020
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
    • Experimental Procedures
    • Results
    • Discussion
    • 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