Influx Mechanism of 2′,3′-Dideoxyinosine and Uridine at the Blood-Placenta Barrier

K. Sato, Y. Sai, Tomohiro Nishimura, T. Chishu, S. Shimpo, N. Kose, E. Nakashima

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 Km values for ddI and uridine of 6.51 mM and 23.4 μM, 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 Xenopus laevis oocytes expressing rat ENT2 was inhibited by 5 mM ddI, in agreement with the results for TR-TBT 18d-1. Our results indicate that ddI and uridine are both taken up in part via ENT2 in TR-TBT 18d-1 cells, and therefore that ENT2 may contribute to their uptake at the BPB.

Original languageEnglish
Pages (from-to)263-269
Number of pages7
JournalPlacenta
Volume30
Issue number3
DOIs
Publication statusPublished - 2009 Mar

Fingerprint

Didanosine
Uridine
Placenta
Nucleosides
Nucleoside Transport Proteins
Fetus
Xenopus laevis
Trophoblasts
Oocytes

Keywords

  • 2′,3′-Dideoxyinosine
  • Blood-placenta barrier
  • Equilibrative nucleoside transporter
  • Uridine

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine
  • Developmental Biology

Cite this

Influx Mechanism of 2′,3′-Dideoxyinosine and Uridine at the Blood-Placenta Barrier. / Sato, K.; Sai, Y.; Nishimura, Tomohiro; Chishu, T.; Shimpo, S.; Kose, N.; Nakashima, E.

In: Placenta, Vol. 30, No. 3, 03.2009, p. 263-269.

Research output: Contribution to journalArticle

Sato, K, Sai, Y, Nishimura, T, Chishu, T, Shimpo, S, Kose, N & Nakashima, E 2009, 'Influx Mechanism of 2′,3′-Dideoxyinosine and Uridine at the Blood-Placenta Barrier', Placenta, vol. 30, no. 3, pp. 263-269. https://doi.org/10.1016/j.placenta.2008.11.022
Sato, K. ; Sai, Y. ; Nishimura, Tomohiro ; Chishu, T. ; Shimpo, S. ; Kose, N. ; Nakashima, E. / Influx Mechanism of 2′,3′-Dideoxyinosine and Uridine at the Blood-Placenta Barrier. In: Placenta. 2009 ; Vol. 30, No. 3. pp. 263-269.
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