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RESEARCH PRODUCT

Caki-1 cells as a model system for the interaction of renally secreted drugs with OCT3.

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<i>Background/Aims:</i> Organic cation transporters (OCT) in the proximal tubules (PTs) participate in the renal secretion of several therapeutic agents. The exact role of OCT3 in renal secretion remains undetermined, partially due to the lack of an appropriate in vitro model system. The current work introduces the PT representative cell line, Caki-1, as a model system for studying the involvement of OCT3 in renal secretion. <i>Methods:</i> Caki-1 cells were characterized for OCT3 expression via real-time RT-PCR and immunocytochemical staining techniques. Uptake kinetics of OCT3 in Caki-1 cells was determined using prototypical substrates and inhibitors. Inhibition of OCT3-mediated uptake via several renally secreted drugs and those specifically of quaternary ammonium structure were determined. <i>Results:</i> OCT3 expression was confirmed at the gene level and subcellular localization to the basolateral membrane (BLM) was illustrated for the first time. Caki-1 cells exhibited trademark kinetics of OCT3 and interacted with all therapeutic agents tested with varying affinities. The apparent IC<sub>50 </sub>values for cimetidine and trimethoprim were pharmacologically relevant. <i>Conclusion:</i> Confirmation for the usefulness of Caki-1 cells as a PT model system for investigations of OCT3 was obtained, a novel BLM localization of OCT3 was possible and relevant interactions between OCT3 and renally secreted drugs were shown.