![[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. 286, Issue 1, 354-361, July 1998
Department of Biopharmaceutical Sciences, University of California,
San Francisco, San Francisco, California
Recently, a polyspecific organic cation transporter, hOCT1, was cloned
from human liver. To date, limited studies examining the functional
characteristics of the transporter have been performed. The purpose of
the present study was to develop a mammalian expression system for
hOCT1 and to characterize the interactions of various compounds with
the cloned transporter. Lipofection was used to transiently transfect
the hOCT1 plasmid DNA in a human cell line, HeLa. We tested the
interaction of an array of organic cations and other compounds with
hOCT1 by determining Ki values in inhibiting C-tetraethylammonium (TEA) transport in the transfected
cells. Transient expression of hOCT1 activity was observed between 24 and 72 hr post-transfection, with maximal expression at approximately 40 hr. TEA transport was temperature dependent and saturable with Vmax and Km
values of 2.89 ± 0.448 nmol/mg protein/30 min and 229 ± 78.4 µM, respectively. 14C-TEA uptake in hOCT1 plasmid
DNA-transfected HeLa cells was trans-stimulated by
unlabeled TEA and 1-methyl-4-phenyl-pyridinium. Organic cations, including clonidine, quinine, quinidine and verapamil (0.1 mM), significantly inhibited 14C-TEA uptake, whereas the organic
anion, p-aminohippuric acid (5 mM), did not. The neutral
compounds, corticosterone (Ki, 7.0 µM) and
midazolam (Ki, 3.7 µM) potently inhibited
14C-TEA uptake. The Ki values of
several compounds in interacting with hOCT1 differed substantially from
the corresponding values for the rat organic cation transporter, rOCT1,
and the human kidney-specific organic cation transporter, hOCT2,
determined in previous studies. Transiently transfected HeLa cells
represent a useful tool in studying the interactions and kinetics of
organic cations and other xenobiotics with hOCT1 and in understanding
the molecular events involved in organic cation transport.
This article has been cited by other articles:
|
|
 |
|
  Z. Yuan, A. Tie, M. Tarnopolsky, and M. Bakovic Genomic organization, promoter activity, and expression of the human choline transporter-like protein 1 Physiol Genomics, September 14, 2006; 26(1): 76 - 90. [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]
|
|
|
|
 |
|
 J. Biermann, D. Lang, V. Gorboulev, H. Koepsell, A. Sindic, R. Schroter, A. Zvirbliene, H. Pavenstadt, E. Schlatter, and G. Ciarimboli Characterization of regulatory mechanisms and states of human organic cation transporter 2 Am J Physiol Cell Physiol, June 1, 2006; 290(6): C1521 - C1531. [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]
|
|
|
|
 |
|
 B. Kwok, A. Yamauchi, R. Rajesan, L. Chan, U. Dhillon, W. Gao, H. Xu, B. Wang, S. Takahashi, J. Semple, et al. Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R793 - R802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Bourdet, J. B. Pritchard, and D. R. Thakker Differential Substrate and Inhibitory Activities of Ranitidine and Famotidine toward Human Organic Cation Transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3) J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1288 - 1297. [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]
|
|
|
|
|
|
V. Gorboulev, N. Shatskaya, C. Volk, and H. Koepsell Subtype-Specific Affinity for Corticosterone of Rat Organic Cation Transporters rOCT1 and rOCT2 Depends on Three Amino Acids within the Substrate Binding Region Mol. Pharmacol., May 1, 2005; 67(5): 1612 - 1619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Thomas, L. Wang, R. E. Clark, and M. Pirmohamed Active transport of imatinib into and out of cells: implications for drug resistance Blood, December 1, 2004; 104(12): 3739 - 3745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hashimoto, S. Narikawa, X.-L. Huang, T. Minematsu, T. Usui, H. Kamimura, and H. Endou CHARACTERIZATION OF THE RENAL TUBULAR TRANSPORT OF ZONAMPANEL, A NOVEL {alpha}-AMINO-3-HYDROXY-5-METHYLISOXAZOLE-4-PROPIONIC ACID RECEPTOR ANTAGONIST, BY HUMAN ORGANIC ANION TRANSPORTERS Drug Metab. Dispos., October 1, 2004; 32(10): 1096 - 1102. [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]
|
|
|
|
|
|
H. Hasannejad, M. Takeda, K. Taki, H. J. Shin, E. Babu, P. Jutabha, S. Khamdang, M. Aleboyeh, M. L. Onozato, A. Tojo, et al. Interactions of Human Organic Anion Transporters with Diuretics J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 1021 - 1029. [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]
|
|
|
|
 |
|
 Y. Shu, M. K. Leabman, B. Feng, L. M. Mangravite, C. C. Huang, D. Stryke, M. Kawamoto, S. J. Johns, J. DeYoung, E. Carlson, et al. Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1 PNAS, May 13, 2003; 100(10): 5902 - 5907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bednarczyk, S. Ekins, J. H. Wikel, and S. H. Wright Influence of Molecular Structure on Substrate Binding to the Human Organic Cation Transporter, hOCT1 Mol. Pharmacol., March 1, 2003; 63(3): 489 - 498. [Abstract] [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]
|
|
|
|
|
|
T. M. Leazer and C. D. Klaassen The Presence of Xenobiotic Transporters in Rat Placenta Drug Metab. Dispos., February 1, 2003; 31(2): 153 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Khamdang, M. Takeda, R. Noshiro, S. Narikawa, A. Enomoto, N. Anzai, P. Piyachaturawat, and H. Endou Interactions of Human Organic Anion Transporters and Human Organic Cation Transporters with Nonsteroidal Anti-Inflammatory Drugs J. Pharmacol. Exp. Ther., November 1, 2002; 303(2): 534 - 539. [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]
|
|
|
|
|
|
A. Enomoto, M. Takeda, M. Shimoda, S. Narikawa, Y. Kobayashi, Y. Kobayashi, T. Yamamoto, T. Sekine, S. H. Cha, T. Niwa, et al. Interaction of Human Organic Anion Transporters 2 and 4 with Organic Anion Transport Inhibitors J. Pharmacol. Exp. Ther., June 1, 2002; 301(3): 797 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kimura, M. Takeda, S. Narikawa, A. Enomoto, K. Ichida, and H. Endou Human Organic Anion Transporters and Human Organic Cation Transporters Mediate Renal Transport of Prostaglandins J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 293 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takeda, S. Khamdang, S. Narikawa, H. Kimura, Y. Kobayashi, T. Yamamoto, S. H. Cha, T. Sekine, and H. Endou Human Organic Anion Transporters and Human Organic Cation Transporters Mediate Renal Antiviral Transport J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 918 - 924. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
L. Zhang, W. Gorset, C. B. Washington, T. F. Blaschke, D. L. Kroetz, and K. M. Giacomini Interactions of HIV Protease Inhibitors with a Human Organic Cation Transporter in a Mammalian Expression System Drug Metab. Dispos., March 1, 2000; 28(3): 329 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Dresser, A. T. Gray, and K. M. Giacomini Kinetic and Selectivity Differences between Rodent, Rabbit, and Human Organic Cation Transporters (OCT1) J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 1146 - 1152. [Abstract] [Full Text]
|
|
|
|
|
|
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., March 1, 1999; 288(3): 1192 - 1198. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Pietig, T. Mehrens, J. R. Hirsch, I. Cetinkaya, H. Piechota, and E. Schlatter Properties and Regulation of Organic Cation Transport in Freshly Isolated Human Proximal Tubules J. Biol. Chem., August 31, 2001; 276(36): 33741 - 33746. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
