title: Interaction of zalcitabine with human organic anion transporter 1.
abstract: 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.
authors.affiliation: College of Pharmacy, Chosun University, Seosuk-dong, Gwangju, Korea.
authors.forename: Ming Ji
authors.initials: MJ
authors.lastname: Jin
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D027362:Organic Anion Transport Protein 1; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine; D010130:p-Aminohippuric Acid