RT Journal Article SR Electronic T1 TRANSPORT OF THE DOPAMINE D2 AGONIST PRAMIPEXOLE BY RAT ORGANIC CATION TRANSPORTERS OCT1 AND OCT2 IN KIDNEY JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 495 OP 499 DO 10.1124/dmd.104.002519 VO 33 IS 4 A1 Naoki Ishiguro A1 Asami Saito A1 Kazutoshi Yokoyama A1 Makoto Morikawa A1 Takashi Igarashi A1 Ikumi Tamai YR 2005 UL http://dmd.aspetjournals.org/content/33/4/495.abstract AB We investigated the mechanism of renal tubular secretion of the dopamine D2 receptor agonist pramipexole in rats, focusing on organic cation transporters 1 and 2. The uptake of [14C]pramipexole by Xenopus oocytes injected with complementary RNA of either rat organic cation transporter (rOCT) 1 or rOCT2 was significantly higher than that by water-injected oocytes: the kinetic parameters, Km and Vmax, of pramipexole uptake were 49.5 μM and 234 pmol/60 min/oocyte for rOCT1, and 16.9 μM and 12.8 pmol/60 min/oocyte for rOCT2. Pramipexole was taken up into kidney slices in a time- and concentration-dependent manner, and Eadie-Hofstee plots revealed the involvement of two saturable components. The kinetic parameters, Km1 and Vmax1, of the high-affinity component were 12.9 μM and 10.7 nmol/15 min/g kidney, respectively. The uptake of [14C]pramipexole by rOCT1, rOCT2, and kidney slices was inhibited by procainamide and corticosterone, which are selective inhibitors of rOCT1 and rOCT2, respectively. The IC50 values of procainamide and corticosterone for the uptake of [14C]pramipexole by rOCT1, rOCT2, and kidney slices were 7.7, 167.0, and 47.0 μM and 163.7, 10.7, and 47.7 μM, respectively. These results demonstrate that both rOCT1 and rOCT2 are involved in the renal uptake of pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The American Society for Pharmacology and Experimental Therapeutics