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The Korean Journal of Pathology 1990;24(4): 430-435.
Kinetics of Cyclosporine uptake on Cultured Human Proximal Tubular Cells.
Jung Young Lee
Department of Pathology, Catholic University Medical College, Seoul, Korea.
ABSTRACT
Cyclosporine A (CSA), a lipophilic cyclic undecapeptide, is not accumulated evently in all tissues and has a high affinity to several tissues such as lymphoid organs, liver, and kidneys. From this point of view, it is reasonable to assume that the amount of CSA uptake would be correlated with the extent of cell injury. On the other hand, verapamil, a Ca2+ channel blocker, bas been shown to ameliorate CSA nephrotoxicity. Since proximal tubule is the major site of drug transport and CSA uptake and its interaction with verapamil in isolated human renal proximal tubular cells. The CSA uptake rapidly increased over the first 5 min and then achieved almost steady-state after 10 min at all concentrations (0.5-10 uM). Kinetic analysis yielded that the Km and Vmax values of CSA were 5.6 uM and 86.2 p mol/mg cell protein/min, respectively. And Ca2+ depletion in media enhanced CSA uptake significantly but verapamil reduced it. These results suggest that the Ca2+ channels and CSA transporting sites on cell membrane are closely associated and that Ca2+ and CSA might be taken up competitively by proximal tubular cells.
Key Words: Cyclosporine A; Verapamil; Kidney; Cultured cell
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