Pharmaceutical Research

, Volume 18, Issue 11, pp 1528–1534 | Cite as

Distinct Characteristics of Organic Cation Transporters, OCT1 and OCT2, in the Basolateral Membrane of Renal Tubules

  • Yumiko Urakami
  • Masahiro Okuda
  • Satohiro Masuda
  • Maiko Akazawa
  • Hideyuki Saito
  • Ken-ich Inui


Purpose. This study was performed to determine the detailed mRNA distribution of organic cation transporters, rOCT1 and rOCT2, along the rat nephron and to distinguish the substrate affinities of these transporters.

Methods. The distributions of rOCT1 and rOCT2 mRNA were determined by reverse transcriptase polymerase chain reaction analysis of microdissected nephron segments. Using MDCK cells transfected with rOCT1 or rOCT2 cDNA, the inhibitory effects of various compounds on the uptake of [14C]tetraethylammonium were assessed.

Results. rOCT1 mRNA was detected primarily in the superficial and juxtamedullary proximal convoluted tubules, whereas rOCT2 mRNA was detected widely in the superficial and juxtamedullary proximal straight and convoluted tubules, medullary thick ascending limbs, distal convoluted tubule, and cortical collecting duct. The IC50 values for cationic drugs and endogenous cations on [14C]tetraethylammonium uptake across the basolateral membranes in the transfectants indicated that rOCT1 and rOCT2 had similar inhibitor specificity for many compounds but showed moderate differences in the specificity for several compounds, such as 1-methyl-4-phenylpyridinium, dopamine, disopyramide, and chlorpheniramine.

Conclusions. rOCT1 and rOCT2 possess similar but not identical multispecificities for various compounds with distinct distributions along the nephron, indicating that the two transporters share physiologic and pharmacologic roles in the renal handling of cationic compounds.

renal tubular secretion basolateral membranes rOCT1 rOCT2 neurotransmitter antiarrhythmic 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. B. Pritchard and D. S. Miller. Mechanisms mediating renal secretion of organic anions and cations. Physiol. Rev. 73:765-796 (1993).Google Scholar
  2. 2.
    K. J. Ullrich. Specificity of transporters for ‘organic anion and organic cation’ in the kidney. Biochim. Biophys. Acta 1197:45-62 (1994).Google Scholar
  3. 3.
    H. Koepsell. Organic cation transporters in intestine, kidney, liver, and brain. Annu. Rev. Physiol. 60:243-266 (1998).Google Scholar
  4. 4.
    K. Inui, S. Masuda, and H. Saito. Cellular and molecular aspects of drug transport in the kidney. Kidney Int. 58:944-958 (2000).Google Scholar
  5. 5.
    D. Gründemann, V. Gorboulev, S. Gambaryan, M. Veyhl, and H. Koepsell. Drug excretion mediated by a new prototype of polyspecific transporter. Nature 372:549-552 (1994).Google Scholar
  6. 6.
    M. Okuda, H. Saito, Y. Urakami, M. Takano, and K. Inui. cDNA cloning and functional expression of a novel rat kidney organic cation transporter, OCT2. Biochem. Biophys. Res Commun. 224: 500-507 (1996).Google Scholar
  7. 7.
    R. Kekuda, P. D. Prasad, X. Wu, H. Wang, Y.-J. Fei, F. H. Leibach, and V. Ganapathy. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J. Biol. Chem. 273:15971-15979 (1998).Google Scholar
  8. 8.
    A. E. Busch, U. Karbach, D. Miska, V. Gorboulev, A. Akhoundova, C. Volk, P. Arndt, J. C. Ulzheimer, M. S. Sonders, C. Baumann, S. Waldegger, F. Lang, and H. Koepsell. Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotrasmitters, amantadine, and memantine. Mol. Pharmacol. 54:342-352 (1998).Google Scholar
  9. 9.
    M. Okuda, Y. Urakami, H. Saito, and K. Inui. Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim. Biophys. Acta. 1417:224-231 (1999).Google Scholar
  10. 10.
    A. E. Busch, S. Quester, J. C. Ulzheimer, S. Waldegger, V. Gorboulev, P. Arndt, F. Lang, and H. Koepsell. Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J. Biol. Chem. 271:32599-32604 (1996).Google Scholar
  11. 11.
    G. Nagel, C. Volk, T. Friedrich, J. C. Ulzheimer, E. Bamberg, and H. Koepsell. A reevaluation of substrate specificity of the rat cation transporter rOCT1. J. Biol. Chem. 272:31953-31956 (1997).Google Scholar
  12. 12.
    F. Martel, T. Vetter, H. Russ, D. Gründemann, I. Azevedo, H. Koepsell, and E. Shömig. Transport of small organic cations in the rat liver: the role of the organic cation transporter OCT1. Naunyn-Schmiedeberg's Arch. Pharmacol. 354:320-326 (1996).Google Scholar
  13. 13.
    U. Karbach, J. Kricke, F. Meyer-Wentrup, V. Gorboulev, C. Volk, D. Loffing-Cueni, B. Kaissling, S. Bachmann, and H. Koepsell. Localization of organic cation transporters OCT1 and OCT2 in rat kidney. Am. J. Physiol. 279:F679-F687 (2000).Google Scholar
  14. 14.
    M. Sugawara-Yokoo, Y. Urakami, H. Koyama, K. Fujikura, S. Masuda, H. Saito, T. Naruse, K. Inui, and K. Takata. Differential localization of organic cation transporters rOCT1 and rOCT2 in the basolateral membrane of rat kidney proximal tubules. Histochem. Cell Biol. 114:175-180 (2000).Google Scholar
  15. 15.
    V. Gorboulev, J. C. Ulzheimer, A. Akhoundova, I. Ulzheimer-Teuber, U. Karbach, S. Quester, C. Baumann, F. Lang, A. E. Busch, and H. Koepsell. Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 16: 871-881 (1997).Google Scholar
  16. 16.
    L. Zhang, M. J. Dresser, A. T. Gray, S. C. Yost, S. Terashita, and K. M. Giacomini. Cloning and functional expression of a human liver organic cation transporter. Mol. Pharmacol. 51:913-921 (1997).Google Scholar
  17. 17.
    D. Gründemann, S. Köster, N. Kiefer, T. Breidert, M. Engelhardt, F. Spitzenberger, N. Obermüller, and E. Schömig. Transport of monoamine transmitters by the organic cation transporter type 2, OCT2. J. Biol. Chem. 273:30915-30920 (1998).Google Scholar
  18. 18.
    L. Zhang, M. E. Schaner, and K. M. Giacomini. Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J. Pharmacol. Exp. Ther. 286:354-361 (1998).Google Scholar
  19. 19.
    Y. Urakami, M. Okuda, S. Masuda, H. Saito, and K. Inui. Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J. Pharmacol. Exp. Ther. 287: 800-805 (1998).Google Scholar
  20. 20.
    Y. Urakami, M. Okuda, S. Saito, and K. Inui. Hormonal regulation of organic cation transporter OCT2 expression in rat kidney. FEBS Lett. 473:173-176 (2000).Google Scholar
  21. 21.
    S. Masuda, H. Saito, H, Nonoguchi, K. Tomita, and K. Inui. mRNA distribution and membrane localization of the OAT-K1 organic anion transporter in rat renal tubules. FEBS Lett. 407: 127-131 (1997).Google Scholar
  22. 22.
    M. M. Bradford. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248-254 (1976).Google Scholar
  23. 23.
    D. P. O'Connell, S. J. Botkin, S. I. Ramos, D. R. Sibley, M. A. Ariano, R. A. Felder, and R. M. Carey. Localization of dopamine D1A receptor protein in rat kidneys. Am. J. Physiol. 268:F1185-F1197 (1995).Google Scholar
  24. 24.
    F. Ibarra, A. Aperia, L. Svensson, A. Eklöf, and P. Greengard. Bidirectional regulation of Na, K+-ATPase activity by dopamine and an α-adrenergic agonist. Proc. Natl. Acad. Sci. USA 90:21-24 (1993).Google Scholar
  25. 25.
    H. Koepsell, V. Gorboulev, and P. Arndt. Molecular pharmacology of organic cation transporters in kidney. J. Membr. Biol. 167:103-117 (1999).Google Scholar
  26. 26.
    W. H. Dantzler, S. H. Wright, V. Chatsudthipong, and O. H. Brokl. Basolateral tetraethylammonium transport in intact tubules: specificity and trans-stimulation. Am. J. Physiol. 261:F386-F392 (1991).Google Scholar
  27. 27.
    L. Zhang, W. Gorset, M. J. Dresser, and K. M. Giacomini. The interaction of n-tetraalkylammonium compounds with a human organic cation transporter, hOCT1. J. Pharmacol. Exp. Ther. 288: 1192-1198 (1999).Google Scholar
  28. 28.
    A. E. Busch, S. Quester, J. C. Ulzheimer, V. Gorboulev, A. Akhoundova, S. Waldegger, F. Lang, and H. Koepsell. Monoamine neurotransmitter transport mediated by the polyspecific cation transporter rOCT1. FEBS Lett. 395:153-156 (1996).Google Scholar
  29. 29.
    D. Gründemann, G. Liebich, N. Kiefer, S. Köster, and E, Schömig. Selective substrates for non-neuronal monoamine transporters. Mol. Pharmacol. 56:1-10 (1999).Google Scholar
  30. 30.
    T. Budimann, E. Bamberg, H. Kopsell, and Nagel, G. Mechanism of electrogenic cation transport by the cloned organic cation transporter 2 from rat. J. Biol. Chem 257:29413-29420 (2000).Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Yumiko Urakami
    • 1
  • Masahiro Okuda
    • 1
  • Satohiro Masuda
    • 1
  • Maiko Akazawa
    • 1
  • Hideyuki Saito
    • 1
  • Ken-ich Inui
    • 1
  1. 1.Department of Pharmacy, Kyoto University Hospital, Faculty of MedicineKyoto UniversitySakyo-ku, KyotoJapan

Personalised recommendations