Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
  • Log out
  • 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
  • Log out
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleMETABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Expression and Functionality of Anti-Human Immunodeficiency Virus and Anticancer Drug Uptake Transporters in Immune Cells

Gerard Minuesa, Sergi Purcet, Itziar Erkizia, Míriam Molina-Arcas, Margarita Bofill, Nuria Izquierdo-Useros, F. Javier Casado, Bonaventura Clotet, Marçal Pastor-Anglada and Javier Martinez-Picado
Journal of Pharmacology and Experimental Therapeutics February 2008, 324 (2) 558-567; DOI: https://doi.org/10.1124/jpet.107.131482
Gerard Minuesa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sergi Purcet
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Itziar Erkizia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Míriam Molina-Arcas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Margarita Bofill
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nuria Izquierdo-Useros
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
F. Javier Casado
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bonaventura Clotet
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marçal Pastor-Anglada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Javier Martinez-Picado
  • 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

Almost all drugs used in anti-human immunodeficiency virus (HIV)-1 and anticancer therapies require membrane proteins to get into the cell to develop their proper activity. Nevertheless, little is known regarding the expression and activity of specific carriers involved in the uptake of these drugs in immune cells. Here, we assessed the mRNA levels, protein expression profile, and activity of the gene families SLC28 (coding for concentrative nucleoside transporters, hCNT1–3), SLC29 (equilibrative nucleoside transporters, hENT1–2), and SLC22 (organic cation transporters, hOCT1–3 and hOCTN1–2). Both hENTs and hCNT2 were abundant in primary lymphocytes, with a preferential activity of hENT1. A significant up-regulation in hENTs expression (100-fold) and activity (30-fold) was seen under stimulation of primary T lymphocytes. In contrast, monocytes, monocyte-derived macrophages (MDMs), and immature monocyte-derived dendritic cells predominantly expressed hCNT3, a functional transporter in MDMs. Finally, in immune cells, hOCTs showed a more heterogeneous expression profile and a lower activity than human nucleoside transporters (hNTs), although up-regulation of hOCTs also occurred upon lymphocyte activation. Overall, the expression and activity of most of the studied transporters emphasize their relevance in relation to anti-HIV and anticancer therapies. The identification of the transporter involved in each specific drug uptake in immune cells could help to optimize pharmacological therapeutic responses.

Footnotes

  • This work has been mostly supported by Grants FIPSE 36372/03 and 36621/06, (jointly to M.P.-A. and J.M.-P.). Additional support was provided by Research Grants SAF2005-01259 (to M.P.-A.) and SAF2004-06991, Marató-TV3 021110, and the Spanish AIDS network “Red Temática Cooperativa de Investigación en Sindrome de Immune Deficiencia Adquirida (SIDA) (G03/173 and RD06/006)” (to J.M.-P.). S.P. was supported by Fundación para la Investigación y la Prevención de SIDA en España, and G.M. was supported by Grant 2005FI-00314 from Agència de Gestic d'Ajuts Universitaris i de Recerca-Generalitat de Catalunya.

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

  • doi:10.1124/jpet.107.131482.

  • ABBREVIATIONS: HIV, human immunodeficiency virus; hCNT, human concentrative nucleoside transporter; hENT, human equilibrative nucleoside transporter; hOAT, human organic anion transporter; hOCT, human organic cation transporter; hOCTN, human organic cation/zwitterion transporter; PHA, phytohemagglutinin; ddC, zalcitabine; ddI, didanosine; IL, interleukin; MDM, monocyte-derived macrophages; D-22, 1,1′-diethyl-2,2′-cyanine iodide; MDDCs, monocyte-derived dendritic cells; NBTI, nitrobenzylthioinosine; DIP, dipyridamole; MPP+, N-methyl-4-phenylpyridinium; ET, ergothioneine; GM-CSF, granulocyte/macrophage colony-stimulating factor; HRP, horseradish peroxidase; AZT, azidothymidine; TBS, Tris-buffered saline; LPS, lipopolysaccharide; PCR, polymerase chain reaction; CT, threshold cycle; mMDDC, mature MDDC; 5′-DFUR, 5′-deoxy-5-fluorouradine; Rani, ranitidine; hNT, human nucleoside transporters; DAB, 3,3′-diaminobenzidine.

    • Received September 10, 2007.
    • Accepted November 26, 2007.
  • 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.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 377 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 377, Issue 2
1 May 2021
  • 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.
Expression and Functionality of Anti-Human Immunodeficiency Virus and Anticancer Drug Uptake Transporters in Immune Cells
(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 ArticleMETABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Expression and Functionality of Anti-Human Immunodeficiency Virus and Anticancer Drug Uptake Transporters in Immune Cells

Gerard Minuesa, Sergi Purcet, Itziar Erkizia, Míriam Molina-Arcas, Margarita Bofill, Nuria Izquierdo-Useros, F. Javier Casado, Bonaventura Clotet, Marçal Pastor-Anglada and Javier Martinez-Picado
Journal of Pharmacology and Experimental Therapeutics February 1, 2008, 324 (2) 558-567; DOI: https://doi.org/10.1124/jpet.107.131482

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleMETABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Expression and Functionality of Anti-Human Immunodeficiency Virus and Anticancer Drug Uptake Transporters in Immune Cells

Gerard Minuesa, Sergi Purcet, Itziar Erkizia, Míriam Molina-Arcas, Margarita Bofill, Nuria Izquierdo-Useros, F. Javier Casado, Bonaventura Clotet, Marçal Pastor-Anglada and Javier Martinez-Picado
Journal of Pharmacology and Experimental Therapeutics February 1, 2008, 324 (2) 558-567; DOI: https://doi.org/10.1124/jpet.107.131482
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike 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

  • HDL Mimetic 4F Modulates Aβ Distribution in Brain and Plasma
  • AOX1 Inhibition by Gefitinib, Erlotinib, and Metabolites
  • Catalytic Activity of CYP2C9 Variants
Show more Metabolism, Transport, and Pharmacogenomics

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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics