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Articles in PresS, published online ahead of print January 28, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00367.2001
Submitted on December 17, 2001
Accepted on January 15, 2002
1 Physiology, University of Arizona, Tucson, AZ, USA
Multiple organic cation (OC) transporters are present in rabbit kidney and may play different functional roles. We cloned rbOCT2 and compared its function with that of rbOCT1. In transiently transfected COS-7 cells, rbOCT1 and rbOCT2 mediated uptake of [3H]tetraethylammonium (TEA) with Kts of 188 and 125 µM, respectively. n-Tetraalkylammonium compounds showed similar affinities for the two homologs, with IC50s for inhibition of OCT1- and OCT2-mediated [3H]TEA transport, respectively (in µM) of: TMA, 4538 and 1395; TPrA, 88.5 and 3.9; TBA, 13.9 and 5.3; and TPeA, 8.8 and 7.6. However, the transporters had very different affinities for cimetidine (CIM): IC50 of 916 µM for rbOCT1 and 5.7 µM for rbOCT2. 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 OC uptake. The median IC50 for CIM inhibition of TEA uptake was 12.3 µM, suggesting that OCT2 is the major contributor to basolateral OC transport in the S2 segment of proximal tubule in rabbit kidney.
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