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• W2141643423 endingPage "658" @default.
• W2141643423 startingPage "647" @default.
• W2141643423 abstract "The purpose of this work was to determine if the sub-bronchial epithelial cell model, Calu-3, expresses the functionally active P-glycoprotein (Pgp) efflux pump. Calu-3 cells express lower levels of Pgp than both Caco-2 and A549 cells as determined by Western Blot analysis. In Calu-3 cells, accumulation of the Pgp substrates rhodamine 123 (Rh123) and calcein acetoxymethyl ester (calcein-AM) was increased in the presence of the specific Pgp inhibitors cyclosporin A (CsA), vinblastine, and taxol. Significant inhibition of Pgp activity was not observed until after 2 h in both cell lines. The organic anion/multidrug resistance associated protein-1 (MRP1) inhibitors, probenecid and indomethacin, did not affect Rh123 accumulation, whereas an increase in calcein accumulation was observed by both agents. The metabolic inhibitor sodium azide decreased the efflux of Rh123 out of Calu-3 cells to the same degree as CsA, supporting inhibition of an active, efflux pathway. The basolateral-to-apical transport of Rh123 was significantly higher than that in the reverse direction, indicating a secretory pathway of efflux that was inhibited 25-fold by CsA. Basolateral-to-apical transport of Rh123 was inhibited slightly with both MRP1 inhibitors; however, no significant effect of Rh123 net secretion was observed. Mixed inhibitor studies demonstrated that Rh123 efflux was mainly Pgp mediated. These results support an energy-dependent Pgp efflux pump pathway that is sensitive to inhibition with CsA in Calu-3 cells. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:647–658, 2001" @default.
• W2141643423 created "2016-06-24" @default.
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• W2141643423 date "2001-05-01" @default.
• W2141643423 modified "2023-09-26" @default.
• W2141643423 title "P-glycoprotein efflux pump expression and activity in Calu-3 cells" @default.
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• W2141643423 doi "https://doi.org/10.1002/1520-6017(200105)90:5<647::aid-jps1021>3.0.co;2-g" @default.
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