Abstract
The plasma membrane distribution and related biological activity of nucleoside transporter proteins (NT) have been 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). Conversely to other epithelia, we have identified the high-affinity pyrimidine-preferring concentrative nucleoside transporter hCNT1 as the only hCNT-type protein expressed at both the basal and apical membranes of this epithelium. hCNT1 localization in lipid rafts is also dependent upon its subcellular localization in the apical plasma membrane, suggesting a complex cellular and regional expression. Overall, this favours 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 IUGR, have been reported.
- Received February 18, 2011.
- Revision received August 8, 2011.
- Accepted August 8, 2011.
- The American Society for Pharmacology and Experimental Therapeutics