Mechanism of nucleoside uptake in rat placenta and induction of placental CNT2 in experimental diabetes

Tomohiro Nishimura, Takuya Chishu, Masatoshi Tomi, Ryo Nakamura, Kazuko Sato, Noriko Kose, Yoshimichi Sai, Emi Nakashima

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The purpose of this study was to clarify the transport characteristics of nucleosides in rat placenta and the changes of functional expression of nucleoside transporters in rat placenta with experimental diabetes mellitus. Placental uptake clearances of [3H]adenosine and [3H]zidovudine from maternal blood was much higher than that of [14C]mannitol. Xenopus oocytes injected with rat ENT1 and ENT2 cRNA took up [3H]adenosine with Km values of 6.1 and 26 μM, respectively. [3H]Adenosine transport by rat placental brush-border membrane vesicles (BBMV) was saturable and was inhibited by nitrobenzylthioinosine (NBMPR), a specific ENT inhibitor, in a manner consistent with involvement of both rat ENT1 and ENT2. [3H]Didanosine was modestly taken up by placenta, and the inhibitory effect of 100 μM NBMPR on [3H]ddI uptake by BBMV suggested a role of ENT2-mediated transport. Expression of ENT1, ENT2, ENT3, CNT2, and CNT3 mRNAs was detected in placenta of control and streptozotocin (STZ)- induced diabetic pregnant rats, and CNT2 (SLC28A2) expression was significantly increased in STZinduced diabetic rats. Consistently, Na+-dependent adenosine uptake by BBMV from STZ-induced diabetic pregnant rats was higher than that from control rats. These results suggest the involvement of placental ENT2 as well as ENT1 in nucleoside uptake from maternal blood, and the induction of CNT2 in experimental diabetes mellitus.

Original languageEnglish
Pages (from-to)439-446
Number of pages8
JournalDrug Metabolism And Pharmacokinetics
Volume27
Issue number4
DOIs
Publication statusPublished - 2012

Keywords

  • Antivirals
  • Diabetes
  • Drug distribution
  • Membrane permeability
  • Nucleosides
  • Placenta
  • SLC28
  • SLC29
  • Transporters

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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