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Transport mechanism of ursodeoxycholic acid in human placental BeWo cells
Author(s) -
Xia Yanming,
Dong Ying,
Zhao Xiaoli,
Di Liuqing,
Li Junsong
Publication year - 2018
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2150
Subject(s) - ursodeoxycholic acid , multidrug resistance associated protein 2 , efflux , apical membrane , organic anion transporting polypeptide , chemistry , organic anion transporter 1 , epithelial polarity , abcg2 , transporter , cholestasis of pregnancy , organic cation transport proteins , membrane transport , ion transporter , pharmacology , biochemistry , fetus , biology , membrane , atp binding cassette transporter , pregnancy , genetics , gene
Abstract Ursodeoxycholic acid (UDCA) is a first‐line drug to treat intrahepatic cholestasis of pregnancy (ICP). However, its effects on the fetus are not clearly known. To better guide its clinical use, we aimed to study the mechanism underlying the placental transport of UDCA. The uptake and efflux of UDCA across placental apical membranes were studied using BeWo cells; effects of different exposure durations, UDCA concentrations, temperatures, and inhibitors of transporters were studied. A transwell assay was performed, and UDCA concentration in both fetal and maternal sides was measured using LC–MS/MS. Higher unidirectional transport of UDCA was observed in the basolateral‐to‐apical direction than in the apical‐to‐basolateral direction. Ko143 and verapamil, which are typical inhibitors of efflux transporters, significantly increased UDCA transport from different directions. UDCA uptake from the apical membrane of BeWo cells was time‐dependent, but sodium‐independent. It was inhibited by inhibitors of energy metabolism and of organic anion transporters, indicating an active transport mechanism. UDCA uptake from the apical membranes of BeWo cells could be mediated by organic anion‐transporting polypeptides, whereas its efflux could be mediated by breast cancer resistance protein and multidrug resistant protein 3. The results of the present study may provide a basis for UDCA use in pregnancy.