TRANSCELLULAR TRANSPORT OF p-AMINOHIPPURATE, AN ORGANIC ANION, IN CULTURED KIDNEY EPITHELIAL CELLS

Drug Metabolism and Pharmacokinetics(1993)

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摘要
Transport of an organic anion, p-aminohippurate (PAH), was investigated in the OK kidney epithelial cell line using the cells grown on permeable supports. Specifically mediated transcellular transport of PAH across OK cell monolayers occurred only from basal side to apical side, and the accumulation of PAH in the cells was much larger from basal side than from apical side. Both the basal-to-apical transport and the accumulation from basal side were temperature dependent, saturable, and inhibited by anion transport inhibitors such as probenecid. In contrast, such a specific transport of PAH was not observed in LLC-PK1 cells. To further characterize the transcellular transport of PAH across OK cell monolayers, PAH transport in apical and basolateral membranes of the cells was studied. Initial uptake of PAH from basal side was much higher than from apical side. In contrast, PAH efflux from the cells to apical side was higher than to basal side. Both uptake from basal side and efflux to apical side were temperature dependent and inhibited by anion transport inhibitors. In addition, basolateral uptake of PAH was inhibited by dicarboxylates. These results suggest that both basolateral and apical transports of PAH are vectorial processes, which results in vectorial, basal-to-apical transport of PAH across OK cell monolayers. PAH/dicarboxylate exchange is probably involved in PAH transport across basolateral membrane in OK cells. Thus, OK cells should provide a potent in vitro model system for the study of active secretion of organic anion in the kidney.
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kidney,organic anion,transport,p-aminohippurate
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