Drug transport in placental barrier -role of transporter and efflux pump-

Abstract

Drug transport mechanism across the placenta is still unknown. The trophoblast that form the placental barrier have an important role in controlling the passage of molecules from mother to fetus. In this study, we investigated that monocarboxylic acids are actively transported from mother to fetus by a monocarboxylic acid transporter on the trophoblast. The human choriocarcinoma cell line, BeWo, was cultured on tissue culture plates. When the cells reached confluence, benzoic acid uptake experiments were performed The uptake of 14C-benzoic acid by BeWo cells was saturated at higher concentrations. The metabolic inhibitors sodium azide and 2, 4-dnitrophenol significantly inhibited the uptake of 14C-benzoic acid by BeWo cells. In addition, various monocarboxylic acids inhibited the uptake of 14C-benzoic acid, whereas dicarboxylic acids dd not affect the uptake. The findings confirm that monocarboxylic acids are transported by a monocarboxylic transporter on BeWo cell monolayers. There are no reports concerning that efflux transport system, such as P-glycoprotein (P-gp), that actively transport agents from the placenta back into the maternal circulation. We also investigated whether efflux transport system in trophoblast occurs. Calcein-AM was used to evaluate the functional activity of the P-gp efflux transport system. The calcein-AM accumulation by BeWo cells was increased significantly in BeWo cells treated with P-gp inhibitors, cyclosporin A, dipyridamole, quinidine and verapamil. The accumulation of 3H-vinblastine which is a substrate of P-gp was also increased by the P-gp inhibitors in BeWo cells. There exists an efflux transport system as P-gp in trophoblast. This efflux system act as one of a placental barrier and may protect the fetus from toxic xenobiotics from maternal circulation.