Toxicological Sciences, Vol 47, 181-186, Copyright © 1999 by Society of Toxicology
BF Pan, DH Sweet, JB Pritchard, R Chen and JA Nelson
A cDNA for the organic cation transporter (rOCT2) of the rat kidney was
inserted into the retroviral plasmid pLXSN. This plasmid was used to stably
transfect NIH3T3 cells. The transfected cell line exhibited an enhanced
rate of tetraethylammonium (TEA) uptake and efflux compared to wild-type
NIH3T3 cells. Uptake of TEA by the transfected cells was markedly reduced
upon incubation at 4 degrees C. When the extracellular pH was lowered from
8.1 to 5.9, uptake was also reduced, suggesting inhibition of rOCT2 by
extracellular protons. The apparent K(m) for TEA in the transfected cells
was 141 microM. The classical organic cation transport inhibitors, cyanine
863 and cimetidine, produced noncompetitive inhibition with apparent Ki
values of 0.81 and 198 microM, respectively. Daunomycin, vinblastine, and
the deoxyadenosine analogs, 2'-deoxytubercidin and 2-chlorodeoxyadenosine,
did not appear to be substrates for rOCT2. However, the anticancer drug,
cisplatin, competitively inhibited TEA uptake by rOCT2 with an apparent Ki
value of 925 microM, suggesting that rOCT2 may play a role in its renal
secretion. In summary, transfected NIH3T3 cells provide a facile system by
which this and other organic ion transporters can be studied.
ARTICLES
A transfected cell model for the renal toxin transporter, rOCT2
Department of Experimental Pediatrics, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
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