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

A Na+-Dependent Nucleoside Transporter in Microglia

MeeRa Hong, Lyanne Schlichter and Reina Bendayan
Journal of Pharmacology and Experimental Therapeutics January 2000, 292 (1) 366-374;
MeeRa Hong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lyanne Schlichter
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Reina Bendayan
  • 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

In the central nervous system, HIV-1 has a defined tropism for brain macrophages and microglia. Nucleoside analog drugs such as zidovudine improve the clinical and neuropsychological functions in HIV-demented patients. Multiple carrier-mediated transport systems can play an important role in the membrane permeation of nucleosides and nucleoside analog drugs in a number of cells. The purpose of this project was to characterize the uptake properties of the pyrimidine nucleoside probe thymidine by a continuous rat microglia cell line (MLS-9) grown as a monolayer on an impermeable substratum. Approximately 50% of thymidine (10 μM) uptake by the monolayer cells was found to be Na+dependent. Kinetics of specific thymidine uptake showed a single saturation system (Km = 44 μM at 37°C) and a Na+/thymidine stoichiometry of 2:1. Pyrimidine and purine nucleoside probes (50 μM) exerted a competitive inhibitory effect on specific thymidine uptake withKi values of 40, 38, 45, and 39 μM for adenosine, uridine, guanosine, and cytidine, respectively. In addition, nucleoside analog drugs significantly decreased specific thymidine uptake, with IC50 values of 135.1 μM for abacavir and 0.6 μM for zidovudine, which inhibited in a noncompetitive manner. These results suggest that a Na+-dependent nucleoside transport system is present in rat microglia and that long-range interactions between antiretroviral nucleoside analog drugs and the nucleoside substrates may occur at the transporter sites.

Footnotes

  • Send reprint requests to: Dr. Reina Bendayan. Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, 19 Russell St., Toronto, Ontario M5S 2S2, Canada. E-mail:r.bendayan{at}utoronto.ca

  • ↵1 This work is supported by a grant from the Ontario HIV Treatment Network, the Canadian Foundation for AIDS Research, and the Medical Research Council (MT-13657). M. Hong is a recipient of an Ontario HIV Treatment Network Studentship Award.

  • ↵2 Current address: Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 2S2, Canada.

  • ↵3 M. Hong, P. Pennefather, L. Schlichter, and R. Bendayan. Transport properties of thymidine by a rat microglia cell line. Abstract selected for presentation at the 100th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, San Antonio, TX, March 1999.

  • ↵4 Current address: The Neuroscience Institute, University Health Network, Toronto, Ontario M5T 2S8 and Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada.

  • Abbreviations:
    CNS
    central nervous system
    NT
    nucleoside transporter
    es
    equilibrative, sensitive to NBMPR inhibition
    NBMPR
    6-(4-nitrobenzyl)-thio-9-β-d-ribofuranosylpurine
    ei
    equilibrative, insensitive to NBMPR
    cif or N1
    concentrative, NBMPR insensitive, accepts formycin B as a permeant
    cit or N2
    concentrative, NBMPR insensitive, common permeant: thymidine
    cib or N3/N4
    concentrative, NBMPR insensitive, broad specificity
    cs or N5
    concentrative, NBMPR sensitive
    BBB
    blood brain barrier
    CSF
    cerebrospinal fluid
    ZDV
    zidovudine
    3TC
    lamivudine
    ddI
    didanosine
    ddC
    zalcitabine
    NMG
    N-methyl-d-glucamine
    • Received June 10, 1999.
    • Accepted September 29, 1999.
  • 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: 292 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 292, Issue 1
1 Jan 2000
  • 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.
A Na+-Dependent Nucleoside Transporter in Microglia
(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

A Na+-Dependent Nucleoside Transporter in Microglia

MeeRa Hong, Lyanne Schlichter and Reina Bendayan
Journal of Pharmacology and Experimental Therapeutics January 1, 2000, 292 (1) 366-374;

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

A Na+-Dependent Nucleoside Transporter in Microglia

MeeRa Hong, Lyanne Schlichter and Reina Bendayan
Journal of Pharmacology and Experimental Therapeutics January 1, 2000, 292 (1) 366-374;
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

  • Chlorogenic Acid Inhibits Breast Cancer Metastasis
  • SNAP25 and mGluRs Control Pathological Tau Release
  • N-Stearoylethanolamine Inhibits Platelet Reactivity
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics