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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCELLULAR AND MOLECULAR

Determinants of Agonist Binding Affinity on Neuronal Nicotinic Receptor β Subunits

Michael J. Parker, Scott C. Harvey and Charles W. Luetje
Journal of Pharmacology and Experimental Therapeutics October 2001, 299 (1) 385-391;
Michael J. Parker
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott C. Harvey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Charles W. Luetje
  • 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 α and β subunits of heteromeric neuronal nicotinic acetylcholine receptors (nAChRs) are thought to contribute “principal” and “complementary” components to the agonist binding site, respectively. At least six loops of amino acid sequence (A, B, and C from α; D, E, and F from β) are involved. We demonstrated previously that receptors containing the β2 subunit had consistently higher affinities for a variety of agonists than β4-containing receptors. For example, the affinity of the α2β2 receptor for epibatidine, ACh, nicotine, and dimethylphenylpiperazinium (DMPP) exceeds that of α2β4 by 9-, 61-, 87-, and 120-fold, respectively. Using saturation and competition analysis of receptors formed by chimeric β subunits coexpressed with α2 inXenopuslaevis oocytes, we have now identified sequence segment 54–63 (corresponding to loop D) as a major determinant of affinity for epibatidine, ACh, nicotine, and DMPP. We then analyzed a series of mutant β2 subunits in which each residue that differs between β2 and β4 in this region was changed from what occurs in β2 to what occurs in β4. The N55S, V56I, and E63T mutations each resulted in a loss of affinity for ACh and nicotine of 3- to 4-fold, whereas the T59K mutation resulted in a 7-fold loss of ACh and nicotine affinity. These mutations had little or no effect on epibatidine and DMPP affinity. The positive charge introduced by the T59K mutation does not appear to underlie loss of agonist affinity, because a similar loss of affinity was observed when a negative charge (T59D) was introduced at this position.

Footnotes

  • ↵1 Present Address: Department of Neuroscience, Duke University, Durham, NC 27710.

  • ↵2 Present Address: ACADIA Pharmaceuticals, Inc., 3911 Sorrento Valley Blvd., San Diego, CA 92121-1402.

  • This work was supported by a grant to C.W.L. from the National Institute on Drug Abuse (DA08102). M.J.P. and S.C.H. were supported in part by T32-HL07188. Portions of this work have been presented in preliminary form [Parker MJ and Luetje CW (1998) Soc Neurosci Abstr24:84].

  • Abbreviations:
    nAChR
    nicotinic acetylcholine receptor
    DMPP
    dimethylphenylpiperazinium
    AChBP
    ACh-binding protein
    nH
    Hill coefficient
    • Received March 19, 2001.
    • Accepted April 11, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 299 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 1
1 Oct 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 Journal of Pharmacology and Experimental Therapeutics 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.
Determinants of Agonist Binding Affinity on Neuronal Nicotinic Receptor β Subunits
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleCELLULAR AND MOLECULAR

Determinants of Agonist Binding Affinity on Neuronal Nicotinic Receptor β Subunits

Michael J. Parker, Scott C. Harvey and Charles W. Luetje
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 385-391;

Citation Manager Formats

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

Share
Research ArticleCELLULAR AND MOLECULAR

Determinants of Agonist Binding Affinity on Neuronal Nicotinic Receptor β Subunits

Michael J. Parker, Scott C. Harvey and Charles W. Luetje
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 385-391;
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CsA downregulates Selenop expression via a STAT3-FoxO1 axis
  • Anisodamine Ameliorates Acute Lung Injury
  • ACE2 Inhibits LPS-Caused Lung Fibrosis
Show more Cellular and Molecular

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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics