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Pharmaceutical Research

, Volume 19, Issue 2, pp 154–161 | Cite as

Proton Gradient-Dependent Transport of Valproic Acid in Human Placental Brush-Border Membrane Vesicles

  • Hiroaki Nakamura
  • Fumihiko Ushigome
  • Noriko Koyabu
  • Shoji Satoh
  • Kiyomi Tsukimori
  • Hitoo Nakano
  • Hisakazu Ohtani
  • Yasufumi SawadaEmail author
Article

Abstract

Purpose. To investigate the transport mechanism of valproic acid across the human placenta, we used human placental brush-border membrane vesicles and compared them with that of lactic acid.

Methods. Transport of [3H]valproic acid and [14C]lactic acid was measured by using human placental brush-border membrane vesicles.

Results. The uptakes of [3H]valproic acid and [14C]lactic acid into brush-border membrane vesicles were greatly stimulated at acidic extravesicular pH. The uptakes of [3H]valproic acid and [14C]lactic acid were inhibited by various fatty acids, p-chloromercuribenzene sulfonate, α-cyano-4-hydroxycinnamate, and FCCP. A kinetic analysis showed that it was saturable, with Michaelis constants (Kt) of 1.04 ± 0.41 mM and 1.71 ± 0.33 mM for [3H]valproic acid and [14C]lactic acid, respectively. Furthermore, lactic acid competitively inhibited [3H]valproic acid uptake and vice versa.

Conclusion. These results suggest that the transport of valproic acid across the microvillous membrane of human placenta is mediated by a proton-linked transport system that also transports lactic acid. However, some inhibitors differentially inhibited the uptakes of [3H]valproic acid and [14C]lactic acid, suggesting that other transport systems may also contribute to the elevated fetal blood concentration of valproic acid in gravida.

human placenta transport mechanism valproic acid lactic acid 

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Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Hiroaki Nakamura
    • 1
  • Fumihiko Ushigome
    • 1
  • Noriko Koyabu
    • 1
  • Shoji Satoh
    • 2
  • Kiyomi Tsukimori
    • 1
  • Hitoo Nakano
    • 1
  • Hisakazu Ohtani
    • 1
  • Yasufumi Sawada
    • 1
    Email author
  1. 1.Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical SciencesKyushu UniversityHigashi-ku, FukuokaJapan
  2. 2.Department of Reproduction and Gynecology, Graduate School of Medical SciencesKyushu UniversityHigashi-ku, FukuokaJapan

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