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  • Title: Interactions of human organic anion as well as cation transporters with indoxyl sulfate.
    Author: Enomoto A, Takeda M, Taki K, Takayama F, Noshiro R, Niwa T, Endou H.
    Journal: Eur J Pharmacol; 2003 Apr 11; 466(1-2):13-20. PubMed ID: 12679137.
    Abstract:
    Various uremic toxicants including indoxyl sulfate exert a number of biological effects on uremic patients. In order to elucidate the molecular mechanisms for the pharmacokinetics of indoxyl sulfate in human, we examined the interactions of human organic anion transporters (human-OATs) and human organic cation transporters (human-OCTs) with indoxyl sulfate using stable transfectants. Indoxyl sulfate inhibited human-OAT1, human-OAT3 and human-OAT4, but not human-OAT2, human-OCT1 and human-OCT2. Kinetic analysis revealed that the K(i) values for human-OAT1, human-OAT3 and human-OAT4 were 22.7, 168.7 and 181.3 microM, respectively. Human-OAT1 and human-OAT3 mediated the uptake of indoxyl sulfate and human-OAT4 mediated not only the uptake but also the efflux of indoxyl sulfate. In conclusion, by comparing the K(i) values with the plasma concentration of unbound indoxyl sulfate, it was predicted that human-OAT1 and human-OAT3 mediate the transport of indoxyl sulfate in vivo. In addition, it was suggested that human-OAT1 and human-OAT3 are involved in the urinary excretion of indoxyl sulfate, the exacerbation of renal dysfunction and the induction of uremic encephalopathy by indoxyl sulfate.
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