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Department of Experimental Pediatrics and Graduate School of Biomedical Sciences, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
Renal secretion of organic cations and anions
are pleiotropic, active processes in mammals. Some nucleosides such as
deoxyadenosine (dAdo), 2-chlorodeoxyadenosine, and azidothymidine are
secreted by human and rodent kidneys. Previous work (J. A. Nelson, J. F. Kuttesch, Jr., and B. H. Herbert. Biochemical
Pharmacology 32: 2323-2327, 1983) indicated a role
for the classic organic cation transporter (OCT) in the secretion of
the dAdo analog, 2'-deoxytubercidin, by mouse kidney. Using
[14C]tetraethylammonium
bromide ([14C]TEA) as
a substrate, we tested several renal cell lines for a
nucleoside-sensitive OCT. American opossum kidney proximal tubule cells
(OK) express a cimetidine-sensitive and metabolic-dependent ability to
efflux TEA. Other classic OCT inhibitors and several nucleosides also
inhibit TEA efflux by these cells in a manner reflecting structural
specificity for the carrier. Inhibition of OCT by nucleosides is not a
universal feature of OCTs, since TEA transport mediated by cloned rat
kidney OCT2 in the Xenopus laevis
oocyte system was not inhibited by the same nucleosides. In conclusion,
OK cells appear to possess an OCT that may also transport some
nucleosides by a novel carrier.
OK cells; tetraethylammonium; 2'-deoxytubercidin; cimetidine; transport
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