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

Research output: Contribution to journalArticle

115 Citations (Scopus)

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

Fingerprint

Vinblastine
Digoxin
P-Glycoprotein
Vincristine
Transcytosis
Progesterone
Trophoblasts
Microvilli
Placenta
Cyclosporine
Membranes
Fetus
Sodium Azide
Choriocarcinoma
Poisons
Verapamil
Molecular Weight
Epithelial Cells
Monoclonal Antibodies
Mothers

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Human placental transport of vinblastine, vincristine, digoxin and progesterone : Contribution of P-glycoprotein. / Ushigome, Fumihiko; Takanaga, Hitomi; Matsuo, Hirotami; Yanai, Shigeaki; Tsukimori, Kiyomi; Nakano, Hitoo; Uchiumi, Takeshi; Nakamura, Takanori; Kuwano, Michihiko; Ohtani, Hisakazu; Sawada, Yasufumi.

In: European Journal of Pharmacology, Vol. 408, No. 1, 10.11.2000, p. 1-10.

Research output: Contribution to journalArticle

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, vol. 408, no. 1, pp. 1-10. https://doi.org/10.1016/S0014-2999(00)00743-3
Ushigome, Fumihiko ; Takanaga, Hitomi ; Matsuo, Hirotami ; Yanai, Shigeaki ; Tsukimori, Kiyomi ; Nakano, Hitoo ; Uchiumi, Takeshi ; Nakamura, Takanori ; Kuwano, Michihiko ; Ohtani, Hisakazu ; Sawada, Yasufumi. / Human placental transport of vinblastine, vincristine, digoxin and progesterone : Contribution of P-glycoprotein. In: European Journal of Pharmacology. 2000 ; Vol. 408, No. 1. pp. 1-10.
@article{16d53e46885346fc9b2254869280982a,
title = "Human placental transport of vinblastine, vincristine, digoxin and progesterone: Contribution of P-glycoprotein",
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.",
author = "Fumihiko Ushigome and Hitomi Takanaga and Hirotami Matsuo and Shigeaki Yanai and Kiyomi Tsukimori and Hitoo Nakano and Takeshi Uchiumi and Takanori Nakamura and Michihiko Kuwano and Hisakazu Ohtani and Yasufumi Sawada",
year = "2000",
month = "11",
day = "10",
doi = "10.1016/S0014-2999(00)00743-3",
language = "English",
volume = "408",
pages = "1--10",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Human placental transport of vinblastine, vincristine, digoxin and progesterone

T2 - Contribution of P-glycoprotein

AU - Ushigome, Fumihiko

AU - Takanaga, Hitomi

AU - Matsuo, Hirotami

AU - Yanai, Shigeaki

AU - Tsukimori, Kiyomi

AU - Nakano, Hitoo

AU - Uchiumi, Takeshi

AU - Nakamura, Takanori

AU - Kuwano, Michihiko

AU - Ohtani, Hisakazu

AU - Sawada, Yasufumi

PY - 2000/11/10

Y1 - 2000/11/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034634387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034634387&partnerID=8YFLogxK

U2 - 10.1016/S0014-2999(00)00743-3

DO - 10.1016/S0014-2999(00)00743-3

M3 - Article

C2 - 11070177

AN - SCOPUS:0034634387

VL - 408

SP - 1

EP - 10

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1

ER -