Cancer Chemotherapy and Pharmacology

, Volume 45, Issue 4, pp 273–278

Human intestinal es nucleoside transporter: molecular characterization and nucleoside inhibitory profiles

  • Pek Yee Lum
  • Leock Y. Ngo
  • Aimee H. Bakken
  • Jashvant D. Unadkat
ORIGINAL ARTICLE

DOI: 10.1007/s002800050040

Cite this article as:
Lum, P., Ngo, L., Bakken, A. et al. Cancer Chemother Pharmacol (2000) 45: 273. doi:10.1007/s002800050040

Abstract

Purpose: To clone and sequence the equilibrative nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporter (es) from the human small intestine and to examine the capacities of nucleosides and nucleoside analogs to inhibit the uptake of uridine by this transporter. Methods: Using PCR, es was cloned from a cDNA library of the human small intestine. The uptake of 3H-uridine (10 μM) by the recombinant es, expressed in Xenopus oocytes, was measured in the presence (2 mM) and absence of nucleosides and nucleoside analogs. Results: The amino acid sequence of this es transporter was identical to that of the human placental es transporter. Uptake of 3H-uridine by this es transporter was inhibitable by 1 μM NBMPR. Removal of the oxygen from the 3′ position or from both the 2′ and 3′ positions, but not from 2′ or 5′ position, resulted in a partial or total loss of the capacity of the nucleosides to inhibit 3H-uridine uptake. No modifications of the adenosine base or of the uridine base (except for 3 and 6 positions on uracil) affected nucleoside inhibitory capacity. Conclusions: The es transporters of the human intestine and placenta are identical in their amino acid sequences. Moreover, the inhibitory profiles of various nucleoside analogs in inhibiting the uptake of uridine by the intestinal es transporter are similar to those obtained with the as-yet-uncloned human erythrocyte es transporter. Collectively, these findings suggest that the es transporter does not appear to be functionally variant in the human placenta, small intestine or erythrocytes.

Key wordses nucleoside transporterUridine uptakeHuman intestineNucleoside analogsAntiviral and anticancer drugsInhibitory profiles

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Pek Yee Lum
    • 1
  • Leock Y. Ngo
    • 1
  • Aimee H. Bakken
    • 2
  • Jashvant D. Unadkat
    • 1
  1. 1.Department of Pharmaceutics, University of Washington, Box 357610, H272 Health Sciences Building, Seattle, WA 98195, USA e-mail: jash@u.washington.edu Tel.: +1-206-5439434; Fax: +1-206-5433204US
  2. 2.Department of Zoology, University of Washington, Seattle, Washington, USAUS