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

The Role of Membrane and Vesicular Monoamine Transporters in the Neurotoxic and Hypothermic Effects of 1-Methyl-4-(2′-aminophenyl)-1,2,3,6-tetrahydropyridine (2′-NH2-MPTP)

Adam L. Numis, Erica L. Unger, Douglas L. Sheridan, Angela C. Chisnell and Anne M. Andrews
Molecular Pharmacology September 2004, 66 (3) 718-727;
Adam L. Numis
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erica L. Unger
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas L. Sheridan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Angela C. Chisnell
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne M. Andrews
  • 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 neurotoxin 1-methyl-4-(2′-aminophenyl)-1,2,3,6-tetrahydropyridine (2′-NH2-MPTP) damages forebrain serotonin (5-HT) and norepinephrine (NE) nerve terminals while sparing striatal dopaminergic innervation. Previous studies suggest that 2′-NH2-MPTP acts by a mechanism that involves uptake by the plasma membrane 5-HT and NE transporters. The present investigation further explores the molecular mechanism of 2′-NH2-MPTP with regard to cellular transport and effects on body temperature. Mice with genetically controlled decreases in serotonin transporter (SERT) expression were studied to corroborate pharmacologic evidence implicating SERT in 2′-NH2-MPTP-induced serotonin neurotoxicity. To investigate whether sequestration by the intracellular vesicular monoamine transporter type 2 (VMAT2) occurs, mice with reduced VMAT2 expression or mice receiving the VMAT2 inhibitor Ro 4-1284 (2-hydroxy-2-ethyl-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydrobenzo[α]chinolizin hydrochloride) were treated with 2′-NH2-MPTP. Body temperature was measured as a function of reduced SERT or VMAT2 expression. 2′-NH2-MPTP caused a 2°C drop in temperature that was attenuated by decreased SERT but not VMAT2. In addition, complete loss of SERT attenuated cortical and hippocampal depletions in 5-HT but not NE. In contrast, mice with a 50% reduction in VMAT2 exhibited similar 5-HT and NE toxicity when compared with wild-type mice at higher doses of 2′-NH2-MPTP, whereas a slight potentiation of toxicity was observed at very low doses of 2′-NH2-MPTP. Pharmacologic inhibition of VMAT2 caused minimal potentiation of neurotransmitter depletions in response to moderate doses of 2′-NH2-MPTP. Thus, 2′-NH2-MPTP seems to be similar to MPTP in its requirement for selective plasma membrane transport and the expression of acute hypothermia; however, unlike MPTP, VMAT2 does not appear to play a major role in the toxic mechanism of 2′-NH2-MPTP.

  • Received January 22, 2004.
  • Accepted June 11, 2004.
  • 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: 66 (3)
Molecular Pharmacology
Vol. 66, Issue 3
1 Sep 2004
  • 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.
The Role of Membrane and Vesicular Monoamine Transporters in the Neurotoxic and Hypothermic Effects of 1-Methyl-4-(2′-aminophenyl)-1,2,3,6-tetrahydropyridine (2′-NH2-MPTP)
(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

The Role of Membrane and Vesicular Monoamine Transporters in the Neurotoxic and Hypothermic Effects of 1-Methyl-4-(2′-aminophenyl)-1,2,3,6-tetrahydropyridine (2′-NH2-MPTP)

Adam L. Numis, Erica L. Unger, Douglas L. Sheridan, Angela C. Chisnell and Anne M. Andrews
Molecular Pharmacology September 1, 2004, 66 (3) 718-727;

Citation Manager Formats

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

Share
Research ArticleArticle

The Role of Membrane and Vesicular Monoamine Transporters in the Neurotoxic and Hypothermic Effects of 1-Methyl-4-(2′-aminophenyl)-1,2,3,6-tetrahydropyridine (2′-NH2-MPTP)

Adam L. Numis, Erica L. Unger, Douglas L. Sheridan, Angela C. Chisnell and Anne M. Andrews
Molecular Pharmacology September 1, 2004, 66 (3) 718-727;
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
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
  • Benzbromarone relaxes airway smooth muscle via BK activation
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