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Research ArticleArticle

TRANSPORT OF THE DOPAMINE D2 AGONIST PRAMIPEXOLE BY RAT ORGANIC CATION TRANSPORTERS OCT1 AND OCT2 IN KIDNEY

Naoki Ishiguro, Asami Saito, Kazutoshi Yokoyama, Makoto Morikawa, Takashi Igarashi and Ikumi Tamai
Drug Metabolism and Disposition April 2005, 33 (4) 495-499; DOI: https://doi.org/10.1124/dmd.104.002519
Naoki Ishiguro
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Asami Saito
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Kazutoshi Yokoyama
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Makoto Morikawa
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Takashi Igarashi
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Ikumi Tamai
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Abstract

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.

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  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.104.002519.

  • ABBREVIATIONS: r, rat; OCT, organic cation transporter; cRNA, complementary RNA; OAT, organic anion transporter; TEA, tetraethylammonium.

    • Received September 27, 2004.
    • Accepted January 3, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 33 (4)
Drug Metabolism and Disposition
Vol. 33, Issue 4
1 Apr 2005
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Research ArticleArticle

TRANSPORT OF THE DOPAMINE D2 AGONIST PRAMIPEXOLE BY RAT ORGANIC CATION TRANSPORTERS OCT1 AND OCT2 IN KIDNEY

Naoki Ishiguro, Asami Saito, Kazutoshi Yokoyama, Makoto Morikawa, Takashi Igarashi and Ikumi Tamai
Drug Metabolism and Disposition April 1, 2005, 33 (4) 495-499; DOI: https://doi.org/10.1124/dmd.104.002519

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Research ArticleArticle

TRANSPORT OF THE DOPAMINE D2 AGONIST PRAMIPEXOLE BY RAT ORGANIC CATION TRANSPORTERS OCT1 AND OCT2 IN KIDNEY

Naoki Ishiguro, Asami Saito, Kazutoshi Yokoyama, Makoto Morikawa, Takashi Igarashi and Ikumi Tamai
Drug Metabolism and Disposition April 1, 2005, 33 (4) 495-499; DOI: https://doi.org/10.1124/dmd.104.002519
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