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 ArticleNEUROPHARMACOLOGY

Effects of Methamphetamine and Lobeline on Vesicular Monoamine and Dopamine Transporter-Mediated Dopamine Release in a Cotransfected Model System

Clare J. Wilhelm, Robert A. Johnson, Paul G. Lysko, Amy J. Eshleman and Aaron Janowsky
Journal of Pharmacology and Experimental Therapeutics September 2004, 310 (3) 1142-1151; DOI: https://doi.org/10.1124/jpet.104.067314
Clare J. Wilhelm
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert A. Johnson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul G. Lysko
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amy J. Eshleman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aaron Janowsky
  • 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

Dopamine (DA) retention and drug-induced release kinetics were characterized in human embryonic kidney (HEK)-293 cells stably coexpressing the human DA transporter (hDAT) and human vesicular monoamine transporter (hVMAT2). Cofunction of hDAT and hVMAT2 caused greater retention of [3H]DA at 20 min (37°C), or 45 min (22°C) compared with cells that were treated with dihydrotetrabenazene (DHTB) to block the hVMAT2. In hDAT- and hVMAT2-coexpressing cells treated with DHTB during [3H]DA loading, methamphetamine (METH)-induced efflux was only 20% of preloaded [3H]DA, compared with 50 to 60% efflux in the absence of DHTB. Interestingly, the presence of DHTB (during release only) increased the potency and efficacy of METH at inducing [3H]DA release (without DHTB: EC50 = 33.8 μM, maximal release 51%; release with DHTB: EC50 = 3.2 μM, maximal release 61%), suggesting that the effects of METH and DHTB on vesicular storage are additive. High concentrations of lobeline induced a statistically significant release of [3H]DA from HEK-hDAT-hVMAT2 cells, but only in the absence of DHTB, suggesting an hVMAT2-mediated effect. Likewise, lobeline did not induce a significant release of [3H]DA from HEK-hDAT cells. The substrates DA and p-tyramine induced robust release of preloaded [3H]DA from cotransfected cells. Cocaine was somewhat effective at blocking substrate-induced [3H]DA efflux. These results suggest that coexpression of the hDAT and hVMAT2 can be used as a model system to distinguish functional pools of DA and to quantify differences in drug effects on DA disposition. In addition, cotransfected cells can be used to determine mechanisms of simultaneous drug interactions at multiple sites.

Footnotes

  • This work was supported by the Department of Veterans Affairs Merit Review and Research Career Scientist Programs (to A.J.), a National Institutes of Health/Veterans Administration interagency agreement (to A.J. and A.E.), and by the Portland Alcohol Research Center (P50AA10760) (to A.E.).

  • doi:10.1124/jpet.104.067314.

  • ABBREVIATIONS: METH, methamphetamine; DA, dopamine; DAT, dopamine transporter; VMAT, vesicular monoamine transporter; hVMAT, human vesicular monoamine transporter; rVMAT, rat vesicular monoamine transporter; HEK, human embryonic kidney; DHTB, dihydrotetrabenazine; MSR, macrophage scavenger receptor; RTI-55, 3β-(4-iodophenyl)tropane-2β-carboxylic acid methyl ester; MAO, monoamine oxidase; COMT, catechol-o-methyl transferase; ANOVA, analysis of variance.

    • Received February 19, 2004.
    • Accepted April 21, 2004.
  • 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: 310 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 310, 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 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.
Effects of Methamphetamine and Lobeline on Vesicular Monoamine and Dopamine Transporter-Mediated Dopamine Release in a Cotransfected Model System
(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 ArticleNEUROPHARMACOLOGY

Effects of Methamphetamine and Lobeline on Vesicular Monoamine and Dopamine Transporter-Mediated Dopamine Release in a Cotransfected Model System

Clare J. Wilhelm, Robert A. Johnson, Paul G. Lysko, Amy J. Eshleman and Aaron Janowsky
Journal of Pharmacology and Experimental Therapeutics September 1, 2004, 310 (3) 1142-1151; DOI: https://doi.org/10.1124/jpet.104.067314

Citation Manager Formats

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

Share
Research ArticleNEUROPHARMACOLOGY

Effects of Methamphetamine and Lobeline on Vesicular Monoamine and Dopamine Transporter-Mediated Dopamine Release in a Cotransfected Model System

Clare J. Wilhelm, Robert A. Johnson, Paul G. Lysko, Amy J. Eshleman and Aaron Janowsky
Journal of Pharmacology and Experimental Therapeutics September 1, 2004, 310 (3) 1142-1151; DOI: https://doi.org/10.1124/jpet.104.067314
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

  • Substituted tryptamine activity at 5-HT receptors & SERT
  • In Vivo SRI-32743 Attenuates Tat Effects on Extracellular DA
  • Kv7 Opener Attenuates Seizures and Cognitive Deficit
Show more Neuropharmacology

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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics