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Am J Physiol Renal Physiol 283: F124-F133, 2002. First published January 29, 2002; doi:10.1152/ajprenal.00367.2001
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Vol. 283, Issue 1, F124-F133, July 2002

Molecular cloning of rabbit organic cation transporter rbOCT2 and functional comparisons with rbOCT1

Xiaohong Zhang, Kristen K. Evans, and Stephen H. Wright

Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona 85724

Multiple organic cation transporters (OCTs) are present in rabbit kidney and may play different functional roles. We cloned rabbit OCT2 (rbOCT2) and compared its function with that of rabbit OCT1 (rbOCT1). In transiently transfected COS-7 cells, rbOCT1 and rbOCT2 mediated uptake of [3H]tetraethylammonium (TEA) with Kt values of 188 and 125 µM, respectively. n-Tetraalkylammonium compounds showed similar affinities for the two homologs, with IC50 values for inhibition of OCT1- and OCT2-mediated [3H]TEA transport, respectively, of 4,538 and 1,395 µM for tetramethylammonium, 88.5 and 3.9 µM for tetrapropylammonium, 13.9 and 5.3 µM for tetrabutylammonium, and 8.8 and 7.6 µM for tetrapentylammonium. However, the transporters had very different affinities for cimetidine (CIM): IC50 of 916 and 5.7 µM for rbOCT1 and rbOCT2, respectively. CIM inhibition of TEA uptake into single S2 segments of rabbit proximal tubule was used to estimate the contributions of OCT1 and OCT2 to basolateral organic cation uptake. The median IC50 for CIM inhibition of TEA uptake was 12.3 µM, suggesting that OCT2 is the major contributor to basolateral organic cation transport in the S2 segment of proximal tubule in rabbit kidney.

kidney; proximal tubule; uptake; tetraethylammonium; rabbit organic cation transporter


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