期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ijms23031203
关键词
OCT; label-free; xCELLigence; MPP+; transport
In this study, a label-free impedance-based transport assay was developed to detect OCT-mediated transport activity and inhibition. The method was effective in both OCT1-3 overexpressing cells and HeLa cells endogenously expressing OCT3, providing a valuable tool for studying drug-drug interactions and identifying potential inhibitors.
The organic cation transporters OCT1-3 (SLC22A1-3) facilitate the transport of cationic endo- and xenobiotics and are important mediators of drug distribution and elimination. Their polyspecific nature makes OCTs highly susceptible to drug-drug interactions (DDIs). Currently, screening of OCT inhibitors depends on uptake assays that require labeled substrates to detect transport activity. However, these uptake assays have several limitations. Hence, there is a need to develop novel assays to study OCT activity in a physiological relevant environment without the need to label the substrate. Here, a label-free impedance-based transport assay is established that detects OCT-mediated transport activity and inhibition utilizing the neurotoxin MPP+. Uptake of MPP+ by OCTs induced concentration-dependent changes in cellular impedance that were inhibited by decynium-22, corticosterone, and Tyrosine Kinase inhibitors. OCT-mediated MPP+ transport activity and inhibition were quantified on both OCT1-3 overexpressing cells and HeLa cells endogenously expressing OCT3. Moreover, the method presented here is a valuable tool to identify novel inhibitors and potential DDI partners for MPP+ transporting solute carrier proteins (SLCs) in general.
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