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

Influence of Tissue Integrity on Pharmacological Phenotypes of Muscarinic Acetylcholine Receptors in the Rat Cerebral Cortex

Abu Syed Md Anisuzzaman, Atsushi Nishimune, Hatsumi Yoshiki, Junsuke Uwada and Ikunobu Muramatsu
Journal of Pharmacology and Experimental Therapeutics October 2011, 339 (1) 186-193; DOI: https://doi.org/10.1124/jpet.111.182857
Abu Syed Md Anisuzzaman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Atsushi Nishimune
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hatsumi Yoshiki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Junsuke Uwada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ikunobu Muramatsu
  • 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 + SI
  • PDF
Loading

Abstract

Distinct pharmacological phenotypes of muscarinic acetylcholine receptors (mAChRs) have been proposed. We compared the pharmacological profiles of mAChRs in intact segments and homogenates of rat cerebral cortex and other tissues by using radioligand binding assays with [3H]N-methylscopolamine ([3H]NMS). Recombinant M1 and M3 mAChRs were also examined. The density of mAChRs detected by [3H]NMS binding to rat cerebral cortex segments and homogenates was the same (approximately 1400 fmol/mg tissue protein), but the dissociation constant of [3H]NMS was significantly different (1400–1700 pM in segments and 260 pM in homogenates). A wide variation in [3H]NMS binding affinity was also observed among the segments of other tissues (ranging from 139 pM in urinary bladder muscle to 1130 pM in the hippocampus). The mAChRs of cerebral cortex were composed of M1, M2, M3, and M4 subtypes, which showed typical subtype pharmacology in the homogenates. However, in the cortex segments the M3 subtype showed a low selectivity for M3 antagonists (darifenacin, solifenacin) and was not distinguished by the M3 antagonists from the other subtypes. Recombinant M1 and M3 mAChRs showed high affinity for [3H]NMS and subtype-specific pharmacology for each tested ligand. The present binding study under conditions where tissue integrity was kept demonstrates a wide variation in [3H]NMS binding affinity among mAChRs of many rat tissues and the presence of an atypical M3 phenotype in the cerebral cortex, suggesting that the pharmacological properties of mAChRs are not necessarily constant, rather they may be significantly modified by tissue integrity and tissue type.

Footnotes

  • This work was supported in part by a Grant-in Aid for Scientific Research and the 21st Centers of Excellence Research Program (Medical Science) from the Japan Society of the Promotion of Science and a grant from the Smoking Research Foundation of Japan. A.S.M.A. is supported by a grant from the Headquarters for the Advancement of High Priority Research, University of Fukui.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.111.182857.

  • ↵Embedded Image The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    mAChR
    muscarinic acetylcholine receptor
    AF-DX 116
    11-([2-[(diethylamino)methyl]-1-piperdinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one
    CHO
    Chinese hamster ovary
    MT-7
    muscarinic toxin 7
    MT-3
    muscarinic toxin 3
    NMS
    N-methylscopolamine.

  • Received April 11, 2011.
  • Accepted June 29, 2011.
  • Copyright © 2011 by 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: 339 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 339, Issue 1
1 Oct 2011
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • 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 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.
Influence of Tissue Integrity on Pharmacological Phenotypes of Muscarinic Acetylcholine Receptors in the Rat Cerebral Cortex
(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

Distinct mAChR Phenotypes in the Rat Cerebral Cortex

Abu Syed Md Anisuzzaman, Atsushi Nishimune, Hatsumi Yoshiki, Junsuke Uwada and Ikunobu Muramatsu
Journal of Pharmacology and Experimental Therapeutics October 1, 2011, 339 (1) 186-193; DOI: https://doi.org/10.1124/jpet.111.182857

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

Distinct mAChR Phenotypes in the Rat Cerebral Cortex

Abu Syed Md Anisuzzaman, Atsushi Nishimune, Hatsumi Yoshiki, Junsuke Uwada and Ikunobu Muramatsu
Journal of Pharmacology and Experimental Therapeutics October 1, 2011, 339 (1) 186-193; DOI: https://doi.org/10.1124/jpet.111.182857
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • ML355 Effects on Platelets
  • H2S Activates Heme-Inhibited mitoBKCa Channels
  • Insulin Regulates Gene Expression of Midnolin
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