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Molecular Pharmacology

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Research ArticleArticle

Expression and Distribution of Nucleoside Transporter Proteins in the Human Syncytiotrophoblast

Ekaitz Errasti-Murugarren, Paula Díaz, Valeria Godoy, Gloria Riquelme and Marçal Pastor-Anglada
Molecular Pharmacology November 2011, 80 (5) 809-817; DOI: https://doi.org/10.1124/mol.111.071837
Ekaitz Errasti-Murugarren
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Paula Díaz
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Valeria Godoy
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Gloria Riquelme
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Marçal Pastor-Anglada
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Abstract

The plasma membrane distribution and related biological activity of nucleoside transporter proteins (NTs) were investigated in human syncytiotrophoblast from term placenta using a variety of approaches, including nucleoside uptake measurements into vesicles from selected plasma membrane domains, NT immunohistochemistry, and subcellular localization (basal, heavy, and light apical membranes as well as raft-enriched membranes from the apical domain). In contrast with other epithelia, in this epithelium, we have identified the high-affinity pyrimidine-preferring human concentrative nucleoside transporter (hCNT) 1 as the only hCNT-type protein expressed at both the basal and apical membranes. hCNT1 localization in lipid rafts is also dependent on its subcellular localization in the apical plasma membrane, suggesting a complex cellular and regional expression. Overall, this result favors the view that the placenta is a pyrimidine-preferring nucleoside sink from both maternal and fetal sides, and hCNT1 plays a major role in promoting pyrimidine salvage and placental growth. This finding may be of pharmacological relevance, because hCNT1 is known to interact with anticancer nucleoside-derived drugs and other molecules, such as nicotine and caffeine, for which a great variety of harmful effects on placental and fetal development, including intrauterine growth retardation, have been reported.

Footnotes

  • This research was supported in part by Fondecyt-Chile [Grants 1070695 and SAF2008-00577] (the former to G.R.); Centro de Investigación Biomédica en Red (an initiative of Instituto de Salud Carlos III); Generalitat de Catalunya [Grant 2009SGR00624] (to M.P.-A.); and the Ministerio de Ciencia e Innovación [Grant AP2003–3938] (to E.E.-M.).

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

    doi:10.1124/mol.111.071837.

  • ABBREVIATIONS:

    h
    human
    CNT
    concentrative nucleoside transporter
    ENT
    equilibrative nucleoside transporter
    NT
    nucleoside transporter protein
    RT
    reverse transcriptase
    PCR
    polymerase chain reaction
    bp
    base pair(s)
    LMVM
    light microvillous membrane
    MVM
    microvillous membrane
    BM
    basement membrane
    NBTI
    nitrobenzylthioinosine
    MES
    morpholinoethanesulfonic acid
    PBS
    phosphate-buffered saline.

  • Received February 18, 2011.
  • Accepted August 8, 2011.
  • Copyright © 2011 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 80 (5)
Molecular Pharmacology
Vol. 80, Issue 5
1 Nov 2011
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Research ArticleArticle

Nucleoside Transporters in Human Placenta

Ekaitz Errasti-Murugarren, Paula Díaz, Valeria Godoy, Gloria Riquelme and Marçal Pastor-Anglada
Molecular Pharmacology November 1, 2011, 80 (5) 809-817; DOI: https://doi.org/10.1124/mol.111.071837

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Research ArticleArticle

Nucleoside Transporters in Human Placenta

Ekaitz Errasti-Murugarren, Paula Díaz, Valeria Godoy, Gloria Riquelme and Marçal Pastor-Anglada
Molecular Pharmacology November 1, 2011, 80 (5) 809-817; DOI: https://doi.org/10.1124/mol.111.071837
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