| 11070177 |
Ushigome F, Takanaga H, Matsuo H, Yanai S, Tsukimori K, Nakano H, Uchiumi T, Nakamura T, Kuwano M, Ohtani H, Sawada Y: Human placental transport of vinblastine, vincristine, digoxin and progesterone: contribution of P-glycoprotein. Eur J Pharmacol. 2000 Nov 10;408(1):1-10.
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. |
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