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

Eur J Pharmacol. 2000 Nov 10;408(1):1-10. doi: 10.1016/s0014-2999(00)00743-3.


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 [(3)H]vinblastine and [(3)H]vincristine into BeWo cells was increased in the presence of a metabolic inhibitor, sodium azide. The basolateral-to-apical transcellular transport of [(3)H]vinblastine, [(3)H]vincristine and [(3)H]digoxin was greater than the apical-to-basolateral transcellular transport. In the presence of cyclosporin A, the basolateral-to-apical transcellular transport of [(3)H]vinblastine, [(3)H]vincristine and [(3)H]digoxin was significantly increased, and the apical-to-basolateral transcellular transport was decreased. The uptake of [(3)H]vinblastine, [(3)H]vincristine and [(3)H]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 [(3)H]vinblastine, [(3)H]vincristine and [(3)H]digoxin into BeWo cells, the uptake of [(3)H]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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Antimetabolites / pharmacology
  • Antineoplastic Agents, Phytogenic / metabolism*
  • Biological Transport, Active
  • Calcium Channel Blockers / pharmacology
  • Cardiotonic Agents / metabolism*
  • Cell Line
  • Digoxin / metabolism*
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Indicators and Reagents
  • Microvilli / metabolism
  • Placenta / metabolism*
  • Pregnancy
  • Progesterone / metabolism*
  • Progesterone / pharmacology
  • Trophoblasts / metabolism
  • Vinblastine / metabolism*
  • Vincristine / metabolism*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antimetabolites
  • Antineoplastic Agents, Phytogenic
  • Calcium Channel Blockers
  • Cardiotonic Agents
  • Immunosuppressive Agents
  • Indicators and Reagents
  • Progesterone
  • Vincristine
  • Vinblastine
  • Digoxin