Interaction of zalcitabine with human organic anion transporter 1.
The present study aimed to investigate the interaction of zalcitabine with human organic anion transporter 1 (hOATI) during renal excretion. Contribution of OAT1 to the renal transport of zalcitabine was examined using the transfected cell lines overexpressing the human organic anion transporter1 (CHO/hOAT1 cells). Zalcitabine exhibited the inhibition effect on the cellular uptake of [3H]-PAH in CHO/hOAT1 cells with an IC50 value of 1.23 mM. Furthermore, the cellular uptake of zalcitabine increased threefold with the enhancement of hOATI activity in CHO/hOAT1 cells, while it was significantly reduced in the presence of OAT1 inhibitors such as ketoprofen, naproxen, PAH and 6-carboxyfluorescein. Those results suggest that hOATI contributes at least in part to the cellular uptake of zalcitabine across the basolateral membrane of proximal tubular cells.
Jin
Ming Ji
MJ
College of Pharmacy, Chosun University, Seosuk-dong, Gwangju, Korea.
Han
Hyo-Kyung
HK
D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism* / Q000652:urine; D016466:CHO Cells; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D006801:Humans; D027362:Organic Anion Transport Protein 1 / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013268:Stimulation, Chemical; D016047:Zalcitabine / Q000494:pharmacology*; D010130:p-Aminohippuric Acid / Q000378:metabolism
D019380:Anti-HIV Agents; D027362:Organic Anion Transport Protein 1; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine; D010130:p-Aminohippuric Acid