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Related Experiment Videos

Nucleoside transport by perfused human placenta

J Dancis1, J Lee, S Mendoza

  • 1Department of Pediatrics, Kaplan Cancer Center, New York University School of Medicine, N.Y. 10016.

Placenta
|September 1, 1993
PubMed
Summary

Human placenta extensively metabolizes nucleosides like thymidine and adenosine. A shared facilitated diffusion system likely handles nucleoside transport, with zidovudine transferring via simple diffusion.

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Area of Science:

  • Perinatal medicine
  • Biochemistry
  • Pharmacology

Background:

  • Nucleoside transport and metabolism are crucial for fetal development.
  • Understanding placental transfer mechanisms is vital for drug safety and efficacy during pregnancy.

Purpose of the Study:

  • To investigate nucleoside transport and metabolism in the human placenta.
  • To characterize the mechanisms of thymidine and adenosine uptake and transfer.
  • To assess the placental transfer of zidovudine.

Main Methods:

  • Utilized the dual perfusion technique to study human placental transport.
  • Employed steady-state and bolus techniques with radiolabeled nucleosides ([3H] thymidine, [3H] adenosine).
  • Used a dual-tracer method ([3H] adenosine/[14C] L-glucose) to calculate uptake rates and employed competitive inhibition studies.

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Main Results:

  • Significant degradation of both thymidine (40-50%) and adenosine (>95%) by the placenta was observed.
  • Nucleoside uptake from maternal and fetal sides was rapid, saturable, and inhibited by nitrosobenzylthioinosine, indicating facilitated diffusion.
  • Thymidine uptake was slower than adenosine, and excess thymidine inhibited adenosine uptake, suggesting a common transporter.
  • Zidovudine did not compete with adenosine uptake, supporting its transfer via simple diffusion.

Conclusions:

  • The human placenta actively metabolizes thymidine and adenosine.
  • A common facilitated diffusion system mediates the transport of nucleosides, including thymidine and adenosine.
  • Zidovudine crosses the placenta via simple diffusion, independent of the nucleoside transporter system.