Apical uptake of choline and cationic drugs in epithelial cell lines derived from human placenta

Many cationic drugs are administered during pregnancy and might enter the fetal circulation by transplacental passage. This study was performed to characterize the apical uptake of choline and several cationic drugs at cultured epithelial cells of the human placenta. Total uptake of [3H]choline in BeWo cells was H(+)-independent and to 65% Na(+)-independent. Uptake rates into both cell lines were saturable with Michaelis-Menten constants (Kt) of 108 microM (BeWo) and 206 microM (JEG-3), respectively. Cationic drugs such as etilefrine, clonidine, ranitidine, diphenhydramine, imipramine and butylscopolamine strongly inhibited the [3H]choline uptake in BeWo cells and in JEG-3 cells, with Ki values ranging from 0.18 to 3.3 mM. In contrast, tetraethylammonium had only little inhibitory effect on [3H]choline uptake. Using high-performance capillary electrophoresis for quantitative analyses, uptake of etilefrine and diphenhydramine into JEG-3 or BeWo cells was measured. Diphenhydramine was transported into JEG-3 cells in a saturable manner with a Kt value of 0.75 mM. In the presence of sodium, diphenhydramine uptake at BeWo cells was inhibited to 69% by the addition of 50 mM choline chloride. Like choline uptake, total diphenhydramine uptake was to 68% Na(+)-independent in BeWo cells. We conclude that in addition to choline, several cationic drugs, in particular diphenhydramine, are taken up by placental epithelial cells from the maternal blood by carrier-mediated processes. Etilefrine, clonidine, ranitidine, diphenhydramine and butylscopolamine interact with the Na(+)-independent placental choline transport system.