抄録
This study was initiated to functionally characterize multidrug resistance associated protein (MRP)-mediated transport across the lung epithelium. Alveolar type II cells were isolated from rabbit lung and cultured on Transwell until forming a tight monolayers. After the cell monolayer was preloaded with monochlorobimane (mBCl) that is metabolized to a fluorescent glutathione conjugate (mBCl-SG), amount of mBCl-SG exported to apical and basal compartments were measured periodically. mBCl-SG was more preferentially exported in the apical direction than in the basolateral direction. Efflux of mBCl-SG from alveolar epithelial cells was significantly inhibited by a MRP inhibitor MK-571. Pharmacokinetic analysis of efflux profiles revealed that increased efflux of mBCl-SG by B[a]P is not due to enhanced MRP activity but simply due to an elevated level of mBCl-SG in the cells. Elevation of the intracellular level of mBCl-SG corresponded well to that of reduced GSH caused by B[a]P pretreatment.
