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dc.contributor.authorYang, Hong
dc.contributor.authorZhou, Shiwei
dc.contributor.authorGuo, Dong
dc.contributor.authorObianom, Obinna N
dc.contributor.authorLi, Qing
dc.contributor.authorShu, Yan
dc.date.accessioned2021-05-05T16:35:05Z
dc.date.available2021-05-05T16:35:05Z
dc.date.issued2021-04-13
dc.identifier.urihttp://hdl.handle.net/10713/15576
dc.description.abstractCoordinated transcellular transport by the uptake via organic cation transporters (OCTs) in concert with the efflux via multidrug and toxin extrusion proteins (MATEs) is an essential system for hepatic and renal drug disposition. Despite their clinical importance, the regulation of OCTs and MATEs remains poorly characterized. It has been reported that cadmium (Cd2+) increase the activities of OCTs while being a substrate of MATEs. Here, we found that human (h) OCT2 protein, as compared with hMATE1, was more active in trafficking between the plasma membrane and cytoplasmic storage pool. Cd2+ exposure could significantly enhance the translocation of hOCT2 and hOCT1, but not hMATE1, to the plasma membrane. We further identified that candesartan, a widely prescribed angiotensin II receptor blocker, behaved similarly toward OCT2 and MATE1 as Cd2+ did. Importantly, Cd2+ and candesartan treatments could lead to an enhanced accumulation of metformin, which is a well-characterized substrate of OCTs/MATEs, in mouse kidney and liver, respectively. Altogether, our studies have uncovered possible divergent regulation of OCTs and MATEs by certain xenobiotics, such as Cd2+ and candesartan due to the different cellular trafficking of these two families of transporter proteins, which might significantly affect drug disposition in the liver and kidney.en_US
dc.description.urihttps://doi.org/10.3390/pharmaceutics13040537en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofPharmaceuticsen_US
dc.subjectcadmiumen_US
dc.subjectcandesartanen_US
dc.subjectkidneyen_US
dc.subjectliveren_US
dc.subjectmultidrug and toxin extrusion proteins (MATEs)en_US
dc.subjectorganic cation transporters (OCTs)en_US
dc.titleDivergent Regulation of OCT and MATE Drug Transporters by Cadmium Exposureen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/pharmaceutics13040537
dc.identifier.pmid33924306
dc.source.volume13
dc.source.issue4
dc.source.countrySwitzerland


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