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(Received for publication, November 18, 1996, and in revised form, January 16, 1997)
From the Department of Pharmacology, University of Heidelberg, Im
Neuenheimer Feld 366, 69120 Heidelberg, Germany
Renal secretion of organic cations involves at
least two distinct transporters, located in the basolateral and apical
membranes of proximal tubule cells. Whereas the basolateral transporter has recently been cloned, sequence information about the apical type
was not yet available.
An organic cation transporter, OCT2p, was cloned from
LLC-PK1 cells, a porcine cell line with properties of
proximal tubular epithelial cells. OCT2p was heterologously expressed
and characterized in human embryonic kidney 293 cells. OCT2p-mediated
uptake of the prototypical organic cation
[14C]tetraethylammonium ([14C]TEA) into 293 cells was saturable. There was a highly significant correlation between
the Ki values for the inhibition of apical
[14C]TEA uptake into LLC-PK1 cells and 293 cells transfected with OCT2p (r = 0.995;
p < 0.001; n = 6). Although OCT2p is
structurally related to OCT1r, the basolateral organic cation
transporter from rat kidney, the transporters could be clearly
discriminated pharmacologically with corticosterone, decynium22, and
O-methylisoprenaline. The findings at hand suggest that
OCT2 corresponds to the apical type of organic cation transporter.
Reverse transcriptase-polymerase chain reaction indicates that mRNA
of OCT1r is limited to non-neuronal tissue, whereas OCT2r, the OCT2p
homologue from rat, was found in both the kidney and central nervous
regions known to be rich in the monoamine transmitter dopamine.
Volume 272, Number 16,
Issue of April 18, 1997
pp. 10408-10413
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
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