Human placental transport of vinblastine, vincristine, digoxin and progesterone: Contribution of P-glycoprotein

Fumihiko Ushigome, Hitomi Takanaga, Hirotami Matsuo, Shigeaki Yanai, Kiyomi Tsukimori, Hitoo Nakano, Takeshi Uchiumi, Takanori Nakamura, Michihiko Kuwano, Hisakazu Ohtani, Yasufumi Sawada

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Abstract

To elucidate the role of P-glycoprotein in human placenta, we examined its expression in placenta, and the transcellular transport and uptake of P-glycoprotein substrates in cultured human placental choriocarcinoma epithelial cells (BeWo cells). The uptake of [3H]vinblastine and [3H]vincristine into BeWo cells was increased in the presence of a metabolic inhibitor, sodium azide. The basolateral-to-apical transcellular transport of [3H]vinblastine, [3H]vincristine and [3H]digoxin was greater than the apical-to-basolateral transcellular transport. In the presence of cyclosporin A, the basolateral-to-apical transcellular transport of [3H]vinblastine, [3H]vincristine and [3H]digoxin was significantly increased, and the apical-to-basolateral transcellular transport was decreased. The uptake of [3H]vinblastine, [3H]vincristine and [3H]digoxin into BeWo cells was significantly enhanced in the presence of several inhibitors, such as verapamil or mouse monoclonal antibody anti-P-glycoprotein MX-MDR (MRK16) as well as cyclosporin A. Although progesterone significantly enhanced the uptake of [3H]vinblastine, [3H]vincristine and [3H]digoxin into BeWo cells, the uptake of [3H]progesterone was not affected by these inhibitors. Immunoblot analysis revealed that P-glycoprotein with a molecular weight of 172 kDa was expressed in BeWo cells and isolated trophoblast cells. Furthermore, P-glycoprotein was detected in human placental brush-border membrane vesicles, but not in human placental basolateral membrane vesicles. In conclusion, these data suggest that P-glycoprotein is expressed on the brush-border membrane (maternal side) of human placental trophoblast cells. P-Glycoprotein is considered to regulate the transfer of several substances including vinblastine, vincristine and digoxin from mother to fetus, and to protect the fetus from toxic substances. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalEuropean Journal of Pharmacology
Volume408
Issue number1
DOIs
Publication statusPublished - Nov 10 2000

All Science Journal Classification (ASJC) codes

  • Pharmacology

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    Ushigome, F., Takanaga, H., Matsuo, H., Yanai, S., Tsukimori, K., Nakano, H., Uchiumi, T., Nakamura, T., Kuwano, M., Ohtani, H., & Sawada, Y. (2000). Human placental transport of vinblastine, vincristine, digoxin and progesterone: Contribution of P-glycoprotein. European Journal of Pharmacology, 408(1), 1-10. https://doi.org/10.1016/S0014-2999(00)00743-3