Document Detail

Characterization of PXR mediated P-glycoprotein regulation in intestinal LS174T cells.
MedLine Citation:
PMID:  20624464     Owner:  NLM     Status:  In-Process    
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 induction, localization and function over this culture period. This model also has application for the screening of drug candidates for effects on oral bioavailability via effects on the subcellular distribution and trafficking of P-gp.
Bhavani Prasad Kota; Van H Tran; John Allen; Mary Bebawy; Basil D Roufogalis
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-17
Journal Detail:
Title:  Pharmacological research : the official journal of the Italian Pharmacological Society     Volume:  62     ISSN:  1096-1186     ISO Abbreviation:  Pharmacol. Res.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8907422     Medline TA:  Pharmacol Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  426-31     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Faculty of Pharmacy, University of Sydney, Camperdown, NSW 2006, Australia.
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