![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 287, Issue 2, 800-805, November 1998
Department of Pharmacy, Kyoto University Hospital, Faculty of
Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
We have isolated a kidney-specific organic cation transporter, rat
OCT2, which is distinct from rat OCT1 (Okuda M, Saito H, Urakami Y,
Takano M and Inui K (1996) Biochem Biophys Res Commun 224:500-507). In our study, the functional characteristics and membrane localization of OCT1 and OCT2 were investigated by uptake
studies using MDCK cells transfected with rat OCT1 or OCT2 cDNA
(MDCK-OCT1 or MDCK-OCT2) and immunological studies. Tetraethylammonium (TEA) uptake by both MDCK-OCT1 and MDCK-OCT2 cells was markedly elevated when TEA was added to the basolateral medium, but not to the
apical medium. Efflux of TEA from MDCK-OCT1 and MDCK-OCT2 cells was not
changed by extracellular pH from 5.4 to 8.4, whereas TEA uptake by both
transfectants was decreased by acidification of extracellular medium.
Apparent Km values for TEA uptake by MDCK-OCT1
and MDCK-OCT2 cells were 38 and 45 µM, respectively. Although various
hydrophilic organic cations such as 1-methyl-4-phenylpyridinium, cimetidine, quinidine, nicotine,
N1-methylnicotinamide and guanidine markedly inhibited TEA
uptake by both MDCK-OCT1 and MDCK-OCT2 cells, there were no significant differences in the apparent inhibition constants
(Ki) against these organic cations between both
transfectants. Furthermore, immunological studies using a polyclonal
antibody against OCT1 revealed that OCT1 was expressed in the
basolateral membranes but not in the brush-border membranes of the rat
kidney. These results suggested that both OCT1 and OCT2 are
basolateral-type organic cation transporters with broad substrate
specificities, mediating tubular secretion of cationic drugs.
This article has been cited by other articles:
|
|
 |
|
  K.-i. Umehara, M. Iwai, Y. Adachi, T. Iwatsubo, T. Usui, and H. Kamimura Hepatic Uptake and Excretion of (-)-N-{2-[(R)-3-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide (YM758), a Novel If Channel Inhibitor, in Rats and Humans Drug Metab. Dispos., June 1, 2008; 36(6): 1030 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zhou, L. Xia, and J. Wang Metformin Transport by a Newly Cloned Proton-Stimulated Organic Cation Transporter (Plasma Membrane Monoamine Transporter) Expressed in Human Intestine Drug Metab. Dispos., October 1, 2007; 35(10): 1956 - 1962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xia, K. Engel, M. Zhou, and J. Wang Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells Am J Physiol Renal Physiol, February 1, 2007; 292(2): F682 - F690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-y. Ohta, K. Inoue, Y. Hayashi, and H. Yuasa Molecular Identification and Functional Characterization of Rat Multidrug and Toxin Extrusion Type Transporter 1 as an Organic Cation/H+ Antiporter in the Kidney Drug Metab. Dispos., November 1, 2006; 34(11): 1868 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Alnouti, J. S. Petrick, and C. D. Klaassen TISSUE DISTRIBUTION AND ONTOGENY OF ORGANIC CATION TRANSPORTERS IN MICE Drug Metab. Dispos., March 1, 2006; 34(3): 477 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Engel and J. Wang Interaction of Organic Cations with a Newly Identified Plasma Membrane Monoamine Transporter Mol. Pharmacol., November 1, 2005; 68(5): 1397 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ishiguro, A. Saito, K. Yokoyama, M. Morikawa, T. Igarashi, and I. Tamai TRANSPORT OF THE DOPAMINE D2 AGONIST PRAMIPEXOLE BY RAT ORGANIC CATION TRANSPORTERS OCT1 AND OCT2 IN KIDNEY Drug Metab. Dispos., April 1, 2005; 33(4): 495 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hukkanen, P. Jacob III, and N. L. Benowitz Metabolism and Disposition Kinetics of Nicotine Pharmacol. Rev., March 1, 2005; 57(1): 79 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Hoffmaster, M. J. Zamek-Gliszczynski, G. M. Pollack, and K. L. R. Brouwer MULTIPLE TRANSPORT SYSTEMS MEDIATE THE HEPATIC UPTAKE AND BILIARY EXCRETION OF THE METABOLICALLY STABLE OPIOID PEPTIDE [D-PENICILLAMINE2,5]ENKEPHALIN Drug Metab. Dispos., February 1, 2005; 33(2): 287 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. L. Miakotina, M. Agassandian, L. Shi, D. C. Look, and R. K. Mallampalli Adenovirus stimulates choline efflux by increasing expression of organic cation transporter-2 Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L93 - L102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Thomas, C. Tikellis, P. Kantharidis, W. C. Burns, M. E. Cooper, and J. M. Forbes The Role of Advanced Glycation in Reduced Organic Cation Transport Associated with Experimental Diabetes J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 456 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Wright and W. H. Dantzler Molecular and Cellular Physiology of Renal Organic Cation and Anion Transport Physiol Rev, July 1, 2004; 84(3): 987 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Grover, D. Buckley, A. R. Buckley, and W. Cacini Reduced Expression of Organic Cation Transporters rOCT1 and rOCT2 in Experimental Diabetes J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 949 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Jonker and A. H. Schinkel Pharmacological and Physiological Functions of the Polyspecific Organic Cation Transporters: OCT1, 2, and 3 (SLC22A1-3) J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 2 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaewmokul, V. Chatsudthipong, K. K. Evans, W. H. Dantzler, and S. H. Wright Functional mapping of rbOCT1 and rbOCT2 activity in the S2 segment of rabbit proximal tubule Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1149 - F1159. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. W. Jonker, E. Wagenaar, S. van Eijl, and A. H. Schinkel Deficiency in the Organic Cation Transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in Mice Abolishes Renal Secretion of Organic Cations Mol. Cell. Biol., November 1, 2003; 23(21): 7902 - 7908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mizuno, T. Niwa, Y. Yotsumoto, and Y. Sugiyama Impact of Drug Transporter Studies on Drug Discovery and Development Pharmacol. Rev., September 1, 2003; 55(3): 425 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Van Bambeke, J.-M. Michot, and P. M. Tulkens Antibiotic efflux pumps in eukaryotic cells: occurrence and impact on antibiotic cellular pharmacokinetics, pharmacodynamics and toxicodynamics J. Antimicrob. Chemother., May 1, 2003; 51(5): 1067 - 1077. [Full Text] [PDF]
|
|
|
|
|
|
B. C. Burckhardt, S. Brai, S. Wallis, W. Krick, N. A. Wolff, and G. Burckhardt Transport of cimetidine by flounder and human renal organic anion transporter 1 Am J Physiol Renal Physiol, March 1, 2003; 284(3): F503 - F509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Goralski, G. Lou, M. T. Prowse, V. Gorboulev, C. Volk, H. Koepsell, and D. S. Sitar The Cation Transporters rOCT1 and rOCT2 Interact with Bicarbonate but Play Only a Minor Role for Amantadine Uptake into Rat Renal Proximal Tubules J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 959 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-S. Wang, J. W. Jonker, Y. Kato, H. Kusuhara, A. H. Schinkel, and Y. Sugiyama Involvement of Organic Cation Transporter 1 in Hepatic and Intestinal Distribution of Metformin J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 510 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fukada, H. Saito, and K.-i. Inui Transport Mechanisms of Nicotine across the Human Intestinal Epithelial Cell Line Caco-2 J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 532 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Urakami, M. Akazawa, H. Saito, M. Okuda, and K.-i. Inui cDNA Cloning, Functional Characterization, and Tissue Distribution of an Alternatively Spliced Variant of Organic Cation Transporter hOCT2 Predominantly Expressed in the Human Kidney J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1703 - 1710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Cova, U. Laforenza, G. Gastaldi, Y. Sambuy, S. Tritto, A. Faelli, and U. Ventura Guanidine Transport across the Apical and Basolateral Membranes of Human Intestinal Caco-2 Cells Is Mediated by Two Different Mechanisms J. Nutr., July 1, 2002; 132(7): 1995 - 2003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, K. K. Evans, and S. H. Wright Molecular cloning of rabbit organic cation transporter rbOCT2 and functional comparisons with rbOCT1 Am J Physiol Renal Physiol, July 1, 2002; 283(1): F124 - F133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Motohashi, Y. Sakurai, H. Saito, S. Masuda, Y. Urakami, M. Goto, A. Fukatsu, O. Ogawa, and K.-i. Inui Gene Expression Levels and Immunolocalization of Organic Ion Transporters in the Human Kidney J. Am. Soc. Nephrol., April 1, 2002; 13(4): 866 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Slitt, N. J. Cherrington, D. P. Hartley, T. M. Leazer, and C. D. Klaassen Tissue Distribution and Renal Developmental Changes in Rat Organic Cation Transporter mRNA levels Drug Metab. Dispos., February 1, 2002; 30(2): 212 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Hill, T. Cihlar, C. Oo, E. S. Ho, K. Prior, H. Wiltshire, J. Barrett, B. Liu, and P. Ward The Anti-Influenza Drug Oseltamivir Exhibits Low Potential to Induce Pharmacokinetic Drug Interactions via Renal Secretion---Correlation of in Vivo and in Vitro Studies Drug Metab. Dispos., January 1, 2002; 30(1): 13 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Sweet, D. S. Miller, and J. B. Pritchard Ventricular Choline Transport. A ROLE FOR ORGANIC CATION TRANSPORTER 2 EXPRESSED IN CHOROID PLEXUS J. Biol. Chem., November 2, 2001; 276(45): 41611 - 41619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shu, C. L. Bello, L. M. Mangravite, B. Feng, and K. M. Giacomini Functional Characteristics and Steroid Hormone-Mediated Regulation of an Organic Cation Transporter in Madin-Darby Canine Kidney Cells J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 392 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Arndt, C. Volk, V. Gorboulev, T. Budiman, C. Popp, I. Ulzheimer-Teuber, A. Akhoundova, S. Koppatz, E. Bamberg, G. Nagel, et al. Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1 Am J Physiol Renal Physiol, September 1, 2001; 281(3): F454 - F468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Jonker, E. Wagenaar, C. A. A. M. Mol, M. Buitelaar, H. Koepsell, J. W. Smit, and A. H. Schinkel Reduced Hepatic Uptake and Intestinal Excretion of Organic Cations in Mice with a Targeted Disruption of the Organic Cation Transporter 1 (Oct1 [Slc22a1]) Gene Mol. Cell. Biol., August 15, 2001; 21(16): 5471 - 5477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Chen, Z. Li, H. Pan, D. L. Murphy, H. Tamir, H. Koepsell, and M. D. Gershon Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters J. Neurosci., August 15, 2001; 21(16): 6348 - 6361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Han, D. H. Sweet, D.-N. Hu, and J. B. Pritchard Characterization of a Novel Cationic Drug Transporter in Human Retinal Pigment Epithelial Cells J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 450 - 457. [Abstract] [Full Text]
|
|
|
|
|
|
D. H. Sweet, D. S. Miller, and J. B. Pritchard Basolateral localization of organic cation transporter 2 in intact renal proximal tubules Am J Physiol Renal Physiol, November 1, 2000; 279(5): F826 - F834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Terada, K. Sawada, T. Ito, H. Saito, Y. Hashimoto, and K.-I. Inui Functional expression of novel peptide transporter in renal basolateral membranes Am J Physiol Renal Physiol, November 1, 2000; 279(5): F851 - F857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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 Renal Physiol, October 1, 2000; 279(4): F679 - F687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Burckhardt and N. A. Wolff Structure of renal organic anion and cation transporters Am J Physiol Renal Physiol, June 1, 2000; 278(6): F853 - F866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ueda, Y. Horibe, K.-J. Kim, and V. H. L. Lee Functional Characterization of Organic Cation Drug Transport in the Pigmented Rabbit Conjunctiva Invest. Ophthalmol. Vis. Sci., March 1, 2000; 41(3): 870 - 876. [Abstract] [Full Text]
|
|
|
|
|
|
D. H. Sweet and J. B. Pritchard rOCT2 is a basolateral potential-driven carrier, not an organic cation/proton exchanger Am J Physiol Renal Physiol, December 1, 1999; 277(6): F890 - F898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wu, W. Huang, P. D. Prasad, P. Seth, D. P. Rajan, F. H. Leibach, J. Chen, S. J. Conway, and V. Ganapathy Functional Characteristics and Tissue Distribution Pattern of Organic Cation Transporter 2 (OCTN2), an Organic Cation/Carnitine Transporter J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1482 - 1492. [Abstract] [Full Text]
|
|
|
|
|
|
K. B. Goralski and D. S. Sitar Tetraethylammonium and Amantadine Identify Distinct Organic Cation Transporters in Rat Renal Cortical Proximal and Distal Tubules J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 295 - 302. [Abstract] [Full Text]
|
|
|
|
|
|
D. Gründemann, G. Liebich, N. Kiefer, S. Köster, and E. Schömig Selective Substrates for Non-Neuronal Monoamine Transporters Mol. Pharmacol., July 1, 1999; 56(1): 1 - 10. [Abstract] [Full Text]
|
|
|
|
|
|
T. Budiman, E. Bamberg, H. Koepsell, and G. Nagel Mechanism of Electrogenic Cation Transport by the Cloned Organic Cation Transporter 2 from Rat J. Biol. Chem., September 15, 2000; 275(38): 29413 - 29420. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
