Characterization of PXR mediated P-glycoprotein regulation in intestinal LS174T cells

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Bhavani Prasad KotaBasil D Roufogalis

Abstract

Intestinal P-glycoprotein (P-gp) is an important target in drug-drug interactions. Pregnane X receptor (PXR) mediates the induction of intestinal P-gp. The LS174T intestinal cell line has been used in several studies as an in vitro tool to identify the effect of PXR inducers on intestinal P-gp expression. In this study we aimed to further characterize this cell line by focusing on the time dependence of P-gp expression, localization and function in the presence of rifampicin, a P-gp inducer. P-gp protein expression was increased in a time and dose dependent manner following exposure of cells to rifampicin (5-50 μM). The induction of P-gp by rifampicin and its inhibition by ketoconazole (an inhibitor of PXR mediated P-gp induction) confirms the suitability of these cells for PXR induction studies. Confocal microscopy showed that P-gp translocated from intracellular compartments to plasma membrane over 7 days in LS174T cells. P-gp function, as established by rhodamine 123 (Rh123) intracellular accumulation, correlated with increasing P-gp expression and plasma membrane localization over this period. Our data demonstrates that LS174T cells provide a suitable in vitro model to test for the effect of PXR inducers/inhibitors on P-gp ...Continue Reading

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Apr 5, 2011·Toxicology·Juan Pablo RigalliViviana Alicia Catania
Jun 12, 2012·European Journal of Pharmacology·Andrew Crowe, Mary Bebawy
Jan 4, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Jamie E MoscovitzLauren M Aleksunes
Jan 20, 2012·Clinical Pharmacokinetics·Shaojun Shi, Ulrich Klotz
Mar 3, 2020·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Zhenyue WangJing Dong
Dec 24, 2019·Acta Pharmaceutica Sinica. B·Yuhua LiHuichang Bi

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