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Vol. 59, Issue 5, 1277-1286, May 2001
Department of Pharmacology and Toxicology (S.H.C., T. S.,
Y. K., H. E.) and Second Department of Surgery (J.F., Y.K.,
T.G.), Kyorin University School of Medicine, Shinkawa, Mitaka, Tokyo,
Japan
A cDNA encoding a multispecific organic anion transporter 3 (hOAT3) was
isolated from a human kidney cDNA library. The hOAT3 cDNA consisted of
2179 base pairs that encoded a 543-amino-acid residue protein with 12 putative transmembrane domains. The deduced amino acid sequence of
hOAT3 showed 36 to 51% identity to those of other members of the OAT
family. Northern blot analysis revealed that hOAT3 mRNA is expressed in
the kidney, brain, and skeletal muscle. When expressed in
Xenopus laevis oocytes, hOAT3 mediated the transport of
estrone sulfate (Km = 3.1 µM),
p-aminohippurate (Km = 87.2 µM), methotrexate (Km = 10.9 µM), and cimetidine (Km = 57.4 µM)
in a sodium-independent manner. hOAT3 also mediated the transport of
dehydroepiandrosterone sulfate, ochratoxin A, PGE2,
estradiol glucuronide, taurocholate, glutarate, cAMP and uric acid.
Estrone sulfate did not show any trans-stimulatory effects on either influx or efflux of [3H]estrone sulfate
via hOAT3. hOAT3 interacted with chemically heterogeneous anionic
compounds, such as nonsteroidal anti-inflammatory drugs, diuretics,
sulfobromophthalein, penicillin G, bile salts and tetraethyl ammonium
bromide. The hOAT3 protein was shown to be localized in the basolateral
membrane of renal proximal tubules and the hOAT3 gene was determined to
be located on the human chromosome 11q12-q13.3 by fluorescent in situ
hybridization analysis. These results suggest an important role of
hOAT3 in the excretion/detoxification of endogenous and exogenous
organic anions in the kidney.
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P. Jutabha, Y. Kanai, M. Hosoyamada, A. Chairoungdua, D. K. Kim, Y. Iribe, E. Babu, J. Y. Kim, N. Anzai, V. Chatsudthipong, et al. Identification of a Novel Voltage-driven Organic Anion Transporter Present at Apical Membrane of Renal Proximal Tubule J. Biol. Chem., July 18, 2003; 278(30): 27930 - 27938. [Abstract] [Full Text] [PDF]
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R. Kikuchi, H. Kusuhara, D. Sugiyama, and Y. Sugiyama Contribution of Organic Anion Transporter 3 (Slc22a8) to the Elimination of p-Aminohippuric Acid and Benzylpenicillin across the Blood-Brain Barrier J. Pharmacol. Exp. Ther., July 1, 2003; 306(1): 51 - 58. [Abstract] [Full Text] [PDF]
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M. Hasegawa, H. Kusuhara, H. Endou, and Y. Sugiyama Contribution of Organic Anion Transporters to the Renal Uptake of Anionic Compounds and Nucleoside Derivatives in Rat J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1087 - 1097. [Abstract] [Full Text] [PDF]
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D. H. Sweet, L. M. S. Chan, R. Walden, X.-P. Yang, D. S. Miller, and J. B. Pritchard Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na+ gradient Am J Physiol Renal Physiol, April 1, 2003; 284(4): F763 - F769. [Abstract] [Full Text] [PDF]
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A. G. Aslamkhan, Y.-H. Han, X.-P. Yang, R. K. Zalups, and J. B. Pritchard Human Renal Organic Anion Transporter 1-Dependent Uptake and Toxicity of Mercuric-Thiol Conjugates in Madin-Darby Canine Kidney Cells Mol. Pharmacol., March 1, 2003; 63(3): 590 - 596. [Abstract] [Full Text] [PDF]
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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]
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 C. E. Wood, K. E. Gridley, and M. Keller-Wood Biological Activity of 17{beta}-Estradiol-3-Sulfate in Ovine Fetal Plasma and Uptake in Fetal Brain Endocrinology, February 1, 2003; 144(2): 599 - 604. [Abstract] [Full Text] [PDF]
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C. E. Groves, L. Munoz, A. Bahn, G. Burckhardt, and S. H. Wright Interaction of Cysteine Conjugates with Human and Rabbit Organic Anion Transporter 1 J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 560 - 566. [Abstract] [Full Text] [PDF]
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B. Ugele, M. V. St-Pierre, M. Pihusch, A. Bahn, and P. Hantschmann Characterization and identification of steroid sulfate transporters of human placenta Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E390 - E398. [Abstract] [Full Text] [PDF]
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Y. Miki, T. Nakata, T. Suzuki, A. D. Darnel, T. Moriya, C. Kaneko, K. Hidaka, Y. Shiotsu, H. Kusaka, and H. Sasano Systemic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5760 - 5768. [Abstract] [Full Text] [PDF]
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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]
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A. Bahn, M. Knabe, Y. Hagos, M. Rodiger, S. Godehardt, D. S. Graber-Neufeld, K. K. Evans, G. Burckhardt, and S. H. Wright Interaction of the Metal Chelator 2,3-Dimercapto-1-propanesulfonate with the Rabbit Multispecific Organic Anion Transporter 1 (rbOAT1) Mol. Pharmacol., November 1, 2002; 62(5): 1128 - 1136. [Abstract] [Full Text] [PDF]
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A. S. Koh, T. A. Simmons-Willis, J. B. Pritchard, S. M. Grassl, and N. Ballatori Identification of a Mechanism by Which the Methylmercury Antidotes N-Acetylcysteine and Dimercaptopropanesulfonate Enhance Urinary Metal Excretion: Transport by the Renal Organic Anion Transporter-1 Mol. Pharmacol., October 1, 2002; 62(4): 921 - 926. [Abstract] [Full Text] [PDF]
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M. Takeda, S. Khamdang, S. Narikawa, H. Kimura, M. Hosoyamada, S. H. Cha, T. Sekine, and H. Endou Characterization of Methotrexate Transport and Its Drug Interactions with Human Organic Anion Transporters J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 666 - 671. [Abstract] [Full Text] [PDF]
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D. H. Sweet, D. S. Miller, J. B. Pritchard, Y. Fujiwara, D. R. Beier, and S. K. Nigam Impaired Organic Anion Transport in Kidney and Choroid Plexus of Organic Anion Transporter 3 (Oat3 (Slc22a8)) Knockout Mice J. Biol. Chem., July 19, 2002; 277(30): 26934 - 26943. [Abstract] [Full Text] [PDF]
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Y. Kobayashi, N. Ohshiro, A. Shibusawa, T. Sasaki, S. Tokuyama, T. Sekine, H. Endou, and T. Yamamoto Isolation, Characterization and Differential Gene Expression of Multispecific Organic Anion Transporter 2 in Mice Mol. Pharmacol., July 1, 2002; 62(1): 7 - 14. [Abstract] [Full Text] [PDF]
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A. Enomoto, M. Takeda, A. Tojo, T. Sekine, S. H. Cha, S. Khamdang, F. Takayama, I. Aoyama, S. Nakamura, H. Endou, et al. Role of Organic Anion Transporters in the Tubular Transport of Indoxyl Sulfate and the Induction of its Nephrotoxicity J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1711 - 1720. [Abstract] [Full Text] [PDF]
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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]
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Y. Nagata, H. Kusuhara, H. Endou, and Y. Sugiyama Expression and Functional Characterization of Rat Organic Anion Transporter 3 (rOat3) in the Choroid Plexus Mol. Pharmacol., May 1, 2002; 61(5): 982 - 988. [Abstract] [Full Text] [PDF]
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C. M. Breen, D. B. Sykes, G. Fricker, and D. S. Miller Confocal imaging of organic anion transport in intact rat choroid plexus Am J Physiol Renal Physiol, May 1, 2002; 282(5): F877 - F885. [Abstract] [Full Text] [PDF]
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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]
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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]
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M. Hasegawa, H. Kusuhara, D. Sugiyama, K. Ito, S. Ueda, H. Endou, and Y. Sugiyama Functional Involvement of Rat Organic Anion Transporter 3 (rOat3; Slc22a8) in the Renal Uptake of Organic Anions J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 746 - 753. [Abstract] [Full Text] [PDF]
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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]
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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]
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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]
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D. S. Miller Nucleoside Phosphonate Interactions with Multiple Organic Anion Transporters in Renal Proximal Tubule J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 567 - 574. [Abstract] [Full Text] [PDF]
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J. M. Pombrio, A. Giangreco, L. Li, M. F. Wempe, M. W. Anders, D. H. Sweet, J. B. Pritchard, and N. Ballatori Mercapturic Acids (N-Acetylcysteine S-Conjugates) as Endogenous Substrates for the Renal Organic Anion Transporter-1 Mol. Pharmacol., November 1, 2001; 60(5): 1091 - 1099. [Abstract] [Full Text]
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