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• W2102364983 abstract "Transporter adaptor protein PDZK1 regulates several influx transporters for xenobiotics and nutrients in small intestine, and their expression on the apical membrane is diminished in <i>pdzk1</i> gene knockout [<i>pdzk1</i>(−/−)] mice. In the present study, we initially attempted to use <i>pdzk1</i>(−/−) mice to functionally identify influx transporters responsible for intestinal absorption of cimetidine. Contrary to our expectation, the plasma concentration of cimetidine after oral administration to <i>pdzk1</i>(−/−) mice was higher than that in wild-type mice, and the double peaks of plasma concentration found in wild-type mice were not observed in <i>pdzk1</i>(−/−) mice. Western blot analysis of intestinal brush-border membranes revealed that expression of breast cancer resistance protein (BCRP) but not of P-glycoprotein is reduced in <i>pdzk1</i>(−/−) mice. This result was compatible with the reduction of apical localization of BCRP in <i>pdzk1</i>(−/−) mice assessed by immunohistochemical analysis. Transcellular transport of cimetidine in the basal-to-apical direction in Madin-Darby canine kidney II (MDCKII) cells stably expressing both BCRP and PDZK1 (MDCKII/BCRP/PDZK1) was higher than that in MDCKII cells stably expressing BCRP (MDCKII/BCRP) cells. Moreover, MDCKII/BCRP/PDZK1 cells are more resistant than MDCKII/BCRP cells to the cytotoxicity of the anticancer agent 7-ethyl-10-hydroxycamptothecin (SN-38), which is a substrate of BCRP. These results were consistent with the higher expression of BCRP on apical membranes in MDCKII/BCRP/PDZK1 cells. Pull-down and immunoprecipitation studies revealed a physical interaction between BCRP and PDZK1. Taken together, these findings demonstrate that PDZK1 plays a pivotal role in the apical localization of BCRP. This is the first identification of a regulatory protein that physically interacts with and regulates BCRP in small intestine in vivo." @default.
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• W2102364983 date "2011-08-04" @default.
• W2102364983 modified "2023-10-14" @default.
• W2102364983 title "PDZK1 Regulates Breast Cancer Resistance Protein in Small Intestine" @default.
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• W2102364983 doi "https://doi.org/10.1124/dmd.111.040295" @default.
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