Influx mechanism of 2',3'-dideoxyinosine and uridine at the blood-placenta barrier

Placenta
K SatoE Nakashima

Abstract

The blood-placenta barrier (BPB) serves to protect the fetus from exposure to toxins, and to transport various nutrients, including nucleosides, and hormones from mother to fetus. It is known that nucleoside transporters contribute to the transfer of nucleosides and nucleoside analogues. 2',3'-Dideoxyinosine (ddI) has a nucleoside structure, and crosses the BPB. Although ddI is a substrate of several transporters, including equilibrative nucleoside transporters (ENT1 and ENT2), the transport mechanism of ddI in the placenta has not yet been characterized. Therefore, the purpose of this study was to clarify the influx mechanisms of ddI from the maternal to the fetal side, and to examine the interaction between ddI and uridine transport at the BPB. We studied ddI and uridine uptakes using a conditionally immortalized rat syncytiotrophoblast cell line, TR-TBT 18d-1, as a BPB model. The ddI uptake was temperature-dependent, Na(+)-independent and saturable. Kinetic analysis yielded K(m) values for ddI and uridine of 6.51 mM and 23.4 microM, respectively. Uridine uptake was inhibited by ENT1 and ENT2 substrates, and ddI uptake was also inhibited by substrates or inhibitors at concentrations that inhibit ENT2. Uridine uptake in Xenopu...Continue Reading

Citations

Feb 23, 2012·Drug Metabolism and Pharmacokinetics·Tomohiro NishimuraEmi Nakashima
May 17, 2011·Journal of Pharmaceutical Sciences·Tomohiro NishimuraEmi Nakashima
Jun 1, 2011·Journal of Pharmaceutical Sciences·Masatoshi TomiEmi Nakashima
Oct 25, 2011·Biochemical and Biophysical Research Communications·Yosuke NakazawaMakoto Takehana
Mar 7, 2014·Biomolecules & Therapeutics·Na-Young LeeYoung-Sook Kang
Dec 17, 2009·Trends in Pharmacological Sciences·Olena KisReina Bendayan
Nov 27, 2014·Frontiers in Pharmacology·Darren M MossAndrew Owen
May 18, 2016·Advanced Drug Delivery Reviews·Camille AlamReina Bendayan
Jun 23, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yoshimichi SaiEmi Nakashima

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