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

Functional and Genetic Diversity in the Concentrative Nucleoside Transporter, CNT1, in Human Populations

Jennifer H. Gray, Lara M. Mangravite, Ryan P. Owen, Thomas J. Urban, Wendy Chan, Elaine J. Carlson, Conrad C. Huang, Michiko Kawamoto, Susan J. Johns, Douglas Stryke, Thomas E. Ferrin and Kathleen M. Giacomini
Molecular Pharmacology March 2004, 65 (3) 512-519; DOI: https://doi.org/10.1124/mol.65.3.512
Jennifer H. Gray
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lara M. Mangravite
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryan P. Owen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas J. Urban
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wendy Chan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elaine J. Carlson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Conrad C. Huang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michiko Kawamoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan J. Johns
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas Stryke
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas E. Ferrin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathleen M. Giacomini
  • 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 concentrative nucleoside transporter, CNT1 (SLC28A1), mediates the cellular uptake of naturally occurring pyrimidine nucleosides and many structurally diverse anticancer and antiviral nucleoside analogs. As a first step toward understanding whether genetic variation in CNT1 contributes to variation in the uptake and disposition of clinically used nucleoside analogs, we determined the haplotype structure and functionally analyzed all coding region variants of CNT1 identified in ethnically diverse populations (100 African Americans, 100 European Americans, 30 Asians, 10 Mexican Americans, and 7 Pacific Islanders) (Leabman et al., 2003). A total of 58 coding region haplotypes were identified using PHASE analysis, 44 of which contained at least one amino acid variant. More than half of the coding region haplotypes were population-specific. Using site-directed mutagenesis, 15 protein-altering CNT1 variants, including one amino acid insertion and one base pair (bp) deletion, were constructed and expressed in Xenopus laevis oocytes. All variant transporters took up [3H]thymidine with the exception of CNT1-Ser546Pro, a rare variant, and CNT1–1153del, a single bp deletion found at a frequency of 3% in the African American population. The bp deletion results in a frame-shift followed by a stop-codon. The anticancer nucleoside analog gemcitabine had a reduced affinity for CNT1-Val189Ile (a common CNT1 variant found at a frequency of 26%) compared with reference CNT1 (IC50 = 13.8 ± 0.60 μM for CNT1-reference and 23.3 ± 1.5 μM for CNT1-Val189Ile, p < 0.05). These data suggest that common genetic variants of CNT1 may contribute to variation in systemic and intracellular levels of anti-cancer nucleoside analogs.

  • Received September 2, 2003.
  • Accepted November 17, 2003.
  • 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: 65 (3)
Molecular Pharmacology
Vol. 65, Issue 3
1 Mar 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.
Functional and Genetic Diversity in the Concentrative Nucleoside Transporter, CNT1, in Human Populations
(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

Functional and Genetic Diversity in the Concentrative Nucleoside Transporter, CNT1, in Human Populations

Jennifer H. Gray, Lara M. Mangravite, Ryan P. Owen, Thomas J. Urban, Wendy Chan, Elaine J. Carlson, Conrad C. Huang, Michiko Kawamoto, Susan J. Johns, Douglas Stryke, Thomas E. Ferrin and Kathleen M. Giacomini
Molecular Pharmacology March 1, 2004, 65 (3) 512-519; DOI: https://doi.org/10.1124/mol.65.3.512

Citation Manager Formats

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

Share
Research ArticleArticle

Functional and Genetic Diversity in the Concentrative Nucleoside Transporter, CNT1, in Human Populations

Jennifer H. Gray, Lara M. Mangravite, Ryan P. Owen, Thomas J. Urban, Wendy Chan, Elaine J. Carlson, Conrad C. Huang, Michiko Kawamoto, Susan J. Johns, Douglas Stryke, Thomas E. Ferrin and Kathleen M. Giacomini
Molecular Pharmacology March 1, 2004, 65 (3) 512-519; DOI: https://doi.org/10.1124/mol.65.3.512
Reddit logo Twitter logo Facebook 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

  • Analgesic Effects and Mechanisms of Licochalcones
  • Induced Fit Ligand Binding to CYP3A4
  • Englerin A Inhibits T-Type Channels
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