Epithelial cells solute import into

An additional in vitro approach that can provide valuable insight into the possible influence on BSEP inhibition of cooperative interactions with other transporters is by studying vectorial transport of probe substrates using transfected ceUs cultured as confluent monolayers in transwell devices. This approach enables quantification of both basal-to-apical transport through the cells and apical efflux. In these studies it is important to use polarized epithelial cells that express distinct apical and basolateral sinusoidal plasma membrane domains and that also exhibit a low level of endogenous expression of transporters other than BSEP that may mediate apical probe substrate efflux. Appropriate cells include dog kidney-derived MDCK cell lines and porcine kidney-derived LLC-PKl cells. It is also necessary to ensure that basolateral solute carriers are present in the cells that mediate probe substrate uptake. This may require coexpression of BSEP and relevant uptake transporter(s). MDCK cell lines... 

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