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.
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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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