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• W2034709241 startingPage "779" @default.
• W2034709241 abstract "P-Glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) constitute a physiologic barrier in the intestine for many of the same substrates. Their expression can be influenced by nuclear receptor NR1I2 (pregnane X receptor; PXR), which acts as a receptor for various endobiotics and xenobiotics. However, P-gp and CYP3A4 are not identical in anatomic localization, suggesting unique as well as shared regulatory mechanisms of gene expression. We used established human colon carcinoma cell lines (LS180 and Caco-2) and measured mRNA and protein levels in cells after exposures to levothyroxine (l-T₄), triiodo-l-thyronine (l-T₃), and rifampin. Results indicate that l-T₄, l-T₃, and rifampin can upregulate the expression of P-gp mRNA and protein in LS180 cells, but only l-T₄ and l-T₃ can produce the same effect in Caco-2 cells, which are relatively lacking in PXR. In addition, l-T₄ and l-T₃ did not affect the expression of CYP3A4 in either cell line. We conclude that P-gp, but not CYP3A4, can be up-regulated by thyroid hormones in vitro by a PXR-independent mechanism. Considering the widespread prescription use of l-T₄ preparations in the older adult population, these results may be important for the clinical consideration of drug-drug interactions mediated by P-gp." @default.
• W2034709241 created "2016-06-24" @default.
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• W2034709241 date "2004-07-16" @default.
• W2034709241 modified "2023-09-25" @default.
• W2034709241 title "LEVOTHYROXINE UP-REGULATES P-GLYCOPROTEIN INDEPENDENT OF THE PREGNANE X RECEPTOR" @default.
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• W2034709241 doi "https://doi.org/10.1124/dmd.32.8.779" @default.
• W2034709241 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15258100" @default.
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