![[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}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PERSPECTIVES IN PHARMACOLOGY
The Netherlands Cancer Institute, Division of Experimental Therapy, Amsterdam, The Netherlands
For the elimination of environmental toxins and metabolic waste products, the body is equipped with a range of broad-specificity transporters that are generally present in the liver, kidney, and intestine. The polyspecific organic cation transporters OCT1, 2, and 3 (SLC22A1-3) mediate the facilitated transport of a variety of structurally diverse organic cations, including many drugs, toxins, and endogenous compounds. OCT1 and OCT2 are found in the basolateral membrane of hepatocytes, enterocytes, and renal proximal tubular cells. OCT3 has a more widespread tissue distribution and is considered to be the major component of the extraneuronal monoamine transport system (or uptake-2), which is responsible for the peripheral elimination of monoamine neurotransmitters. Studies with knockout mouse models have directly demonstrated that these transporters can have a major impact on the pharmacological behavior of various substrate organic cations. The recent identification of polymorphic genetic variants of human OCT1 and OCT2 that severely affect transport activity thus suggests that some of the interpatient differences in response and sensitivity to cationic drugs may be caused by variable activity of these transporters.
Address correspondence to: Dr. Johan W. Jonker, Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. E-mail: h.jonker{at}nki.nl
This article has been cited by other articles:
|
|
 |
|
  R. Josse, C. Aninat, D. Glaise, J. Dumont, V. Fessard, F. Morel, J.-M. Poul, C. Guguen-Guillouzo, and A. Guillouzo Long-Term Functional Stability of Human HepaRG Hepatocytes and Use for Chronic Toxicity and Genotoxicity Studies Drug Metab. Dispos., June 1, 2008; 36(6): 1111 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsuzaki, T. Morisaki, W. Sugimoto, K. Yokoo, D. Sato, H. Nonoguchi, K. Tomita, T. Terada, K.-i. Inui, A. Hamada, et al. Altered Pharmacokinetics of Cationic Drugs Caused by Down-Regulation of Renal Rat Organic Cation Transporter 2 (Slc22a2) and Rat Multidrug and Toxin Extrusion 1 (Slc47a1) in Ischemia/Reperfusion-Induced Acute Kidney Injury Drug Metab. Dispos., April 1, 2008; 36(4): 649 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hilgendorf, G. Ahlin, A. Seithel, P. Artursson, A.-L. Ungell, and J. Karlsson Expression of Thirty-six Drug Transporter Genes in Human Intestine, Liver, Kidney, and Organotypic Cell Lines Drug Metab. Dispos., August 1, 2007; 35(8): 1333 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, S. Zhang, M. Sorani, and K. M. Giacomini Transport of Paraquat by Human Organic Cation Transporters and Multidrug and Toxic Compound Extrusion Family J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 695 - 700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-i. Asaka, T. Terada, K. Ogasawara, T. Katsura, and K.-i. Inui Characterization of the Basal Promoter Element of Human Organic Cation Transporter 2 Gene J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 684 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Kang, I.-S. Song, H. J. Shin, W.-Y. Kim, C.-H. Lee, J.-C. Shim, H.-H. Zhou, S. S. Lee, and J.-G. Shin Identification and Functional Characterization of Genetic Variants of Human Organic Cation Transporters in a Korean Population Drug Metab. Dispos., April 1, 2007; 35(4): 667 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Watanabe, Y. Kato, T. Sugiura, Y. Kubo, T. Wakayama, S. Iseki, and A. Tsuji PDZ Adaptor Protein PDZK2 Stimulates Transport Activity of Organic Cation/Carnitine Transporter OCTN2 by Modulating Cell Surface Expression Drug Metab. Dispos., November 1, 2006; 34(11): 1927 - 1934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yonezawa, S. Masuda, S. Yokoo, T. Katsura, and K.-i. Inui Cisplatin and Oxaliplatin, but Not Carboplatin and Nedaplatin, Are Substrates for Human Organic Cation Transporters (SLC22A1-3 and Multidrug and Toxin Extrusion Family) J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 879 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Jigorel, M. Le Vee, C. Boursier-Neyret, Y. Parmentier, and O. Fardel Differential Regulation of Sinusoidal and Canalicular Hepatic Drug Transporter Expression by Xenobiotics Activating Drug-Sensing Receptors in Primary Human Hepatocytes Drug Metab. Dispos., October 1, 2006; 34(10): 1756 - 1763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhang, K. S. Lovejoy, J. E. Shima, L. L. Lagpacan, Y. Shu, A. Lapuk, Y. Chen, T. Komori, J. W. Gray, X. Chen, et al. Organic Cation Transporters Are Determinants of Oxaliplatin Cytotoxicity. Cancer Res., September 1, 2006; 66(17): 8847 - 8857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Gasser, C. A. Lowry, and M. Orchinik Corticosterone-Sensitive Monoamine Transport in the Rat Dorsomedial Hypothalamus: Potential Role for Organic Cation Transporter 3 in Stress-Induced Modulation of Monoaminergic Neurotransmission. J. Neurosci., August 23, 2006; 26(34): 8758 - 8766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. White, V. A. Saunders, P. Dang, J. Engler, A. C. W. Zannettino, A. C. Cambareri, S. R. Quinn, P. W. Manley, and T. P. Hughes OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib Blood, July 15, 2006; 108(2): 697 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Boivin, C. Lavoie, G. Vaniotis, A. Baragli, L.-R. Villeneuve, N. Ethier, P. Trieu, B. G. Allen, and T. E. Hebert Functional {beta}-adrenergic receptor signalling on nuclear membranes in adult rat and mouse ventricular cardiomyocytes Cardiovasc Res, July 1, 2006; 71(1): 69 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Michel, Z. Yuan, S. Ramsubir, and M. Bakovic Choline Transport for Phospholipid Synthesis. Experimental Biology and Medicine, May 1, 2006; 231(5): 490 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Saborowski, G. A. Kullak-Ublick, and J. J. Eloranta The Human Organic Cation Transporter-1 Gene Is Transactivated by Hepatocyte Nuclear Factor-4{alpha} J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 778 - 785. [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]
|
|
|
|
 |
|
 X. Zhang, N. V. Shirahatti, D. Mahadevan, and S. H. Wright A Conserved Glutamate Residue in Transmembrane Helix 10 Influences Substrate Specificity of Rabbit OCT2 (SLC22A2) J. Biol. Chem., October 14, 2005; 280(41): 34813 - 34822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Jigorel, M. Le Vee, C. Boursier-Neyret, M. Bertrand, and O. Fardel FUNCTIONAL EXPRESSION OF SINUSOIDAL DRUG TRANSPORTERS IN PRIMARY HUMAN AND RAT HEPATOCYTES Drug Metab. Dispos., October 1, 2005; 33(10): 1418 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Schneider, F. Machavoine, J.-M. Pleau, A.-F. Bertron, R. L. Thurmond, H. Ohtsu, T. Watanabe, A. H. Schinkel, and M. Dy Organic cation transporter 3 modulates murine basophil functions by controlling intracellular histamine levels J. Exp. Med., August 1, 2005; 202(3): 387 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M Beringer and R. L Slaughter Transporters and Their Impact on Drug Disposition Ann. Pharmacother., June 1, 2005; 39(6): 1097 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Suhre, S. Ekins, C. Chang, P. W. Swaan, and S. H. Wright Molecular Determinants of Substrate/Inhibitor Binding to the Human and Rabbit Renal Organic Cation Transporters hOCT2 and rbOCT2 Mol. Pharmacol., April 1, 2005; 67(4): 1067 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kato, Y. Sai, K. Yoshida, C. Watanabe, T. Hirata, and A. Tsuji PDZK1 Directly Regulates the Function of Organic Cation/Carnitine Transporter OCTN2 Mol. Pharmacol., March 1, 2005; 67(3): 734 - 743. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
