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(Received for publication, July 30, 1997, and in revised form, September 19, 1997)
From the Laboratory of Pharmacology and Chemistry, NIEHS, National
Institutes of Health, Research Triangle Park,
North Carolina 27709
Expression cloning in Xenopus laevis
oocytes was used to isolate an organic anion transport protein from rat
kidney. A cDNA library was constructed from size-fractionated
poly(A)+ RNA and screened for probenecid-sensitive
transport of p-aminohippurate (PAH). A 2,227-base pair
cDNA clone containing a 1,656-base pair open reading frame coding
for a peptide 551 amino acids long was isolated and named ROAT1.
ROAT1-mediated transport of 50 µM [3H]PAH
was independent of imposed changes in membrane potential. Transport was
significantly inhibited at 4 °C, or upon incubation with other
organic anions, but not by the organic cation tetraethylammonium, by the multidrug resistance ATPase inhibitor cyclosporin A, or by
urate. External glutarate and
Volume 272, Number 48,
Issue of November 28, 1997
pp. 30088-30095
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Expression Cloning and Characterization of ROAT1
THE BASOLATERAL ORGANIC ANION TRANSPORTER IN RAT KIDNEY
-ketoglutarate (1 mM),
both counterions for basolateral PAH exchange, also inhibited
transport, suggesting that ROAT1 is functionally similar to the
basolateral PAH carrier. Consistent with this conclusion, PAH uptake
was trans-stimulated in oocytes preloaded with
glutarate, whereas the dicarboxylate methylsuccinate, which is not
accepted by the basolateral exchanger, did not
trans-stimulate. Finally, ROAT1-mediated PAH transport was
saturable, with an estimated Km of 70 µM. Each of these properties is identical to those
previously described for the basolateral -ketoglutarate/PAH
exchanger in isolated membrane vesicles or intact renal tubules.
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S. M. Grassl Urate/alpha -ketoglutarate exchange in avian basolateral membrane vesicles Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1144 - C1154. [Abstract] [Full Text] [PDF]
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A. Enomoto, M. F. Wempe, H. Tsuchida, H. J. Shin, S. H. Cha, N. Anzai, A. Goto, A. Sakamoto, T. Niwa, Y. Kanai, et al. Molecular Identification of a Novel Carnitine Transporter Specific to Human Testis. INSIGHTS INTO THE MECHANISM OF CARNITINE RECOGNITION J. Biol. Chem., September 20, 2002; 277(39): 36262 - 36271. [Abstract] [Full Text] [PDF]
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Y. Kato, K. Kuge, H. Kusuhara, P. J. Meier, and Y. Sugiyama Gender Difference in the Urinary Excretion of Organic Anions in Rats J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 483 - 489. [Abstract] [Full Text] [PDF]
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C. Sauvant, H. Holzinger, and M. Gekle Short-Term Regulation of Basolateral Organic Anion Uptake in Proximal Tubular OK cells: EGF Acts via MAPK, PLA2, and COX1 J. Am. Soc. Nephrol., August 1, 2002; 13(8): 1981 - 1991. [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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 Y. L. Zhao, X. B. Cen, M. Ito, K. Yokoyama, K. Takagi, K. Kitaichi, M. Nadai, M. Ohta, K. Takagi, and T. Hasegawa Shiga-Like Toxin II Derived from Escherichia coli O157:H7 Modifies Renal Handling of Levofloxacin in Rats Antimicrob. Agents Chemother., May 1, 2002; 46(5): 1522 - 1528. [Abstract] [Full Text] [PDF]
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S. C. N. Buist, N. J. Cherrington, S. Choudhuri, D. P. Hartley, and C. D. Klaassen Gender-Specific and Developmental Influences on the Expression of Rat Organic Anion Transporters J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 145 - 151. [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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R. Kojima, T. Sekine, M. Kawachi, S. H. Cha, Y. Suzuki, and H. Endou Immunolocalization of Multispecific Organic Anion Transporters, OAT1, OAT2, and OAT3, in Rat Kidney J. Am. Soc. Nephrol., April 1, 2002; 13(4): 848 - 857. [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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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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 G. Lee, S. Dallas, M. Hong, and R. Bendayan Drug Transporters in the Central Nervous System: Brain Barriers and Brain Parenchyma Considerations Pharmacol. Rev., December 1, 2001; 53(4): 569 - 596. [Abstract] [Full Text] [PDF]
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F. Islinger, M. Gekle, and S. H. Wright Interaction of 2,3-Dimercapto-1-propane Sulfonate with the Human Organic Anion Transporter hOAT1 J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 741 - 747. [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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A. Takeuchi, S. Masuda, H. Saito, T. Abe, and K.-i. Inui Multispecific Substrate Recognition of Kidney-Specific Organic Anion Transporters OAT-K1 and OAT-K2 J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 261 - 267. [Abstract] [Full Text] [PDF]
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N. A. WOLFF, B. GRUNWALD, B. FRIEDRICH, F. LANG, S. GODEHARDT, and G. BURCKHARDT Cationic Amino Acids Involved in Dicarboxylate Binding of the Flounder Renal Organic Anion Transporter J. Am. Soc. Nephrol., October 1, 2001; 12(10): 2012 - 2018. [Abstract] [Full Text] [PDF]
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N. Morita, H. Kusuhara, T. Sekine, H. Endou, and Y. Sugiyama Functional Characterization of Rat Organic Anion Transporter 2 in LLC-PK1 Cells J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1179 - 1184. [Abstract] [Full Text] [PDF]
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D. H. Sweet, K. T. Bush, and S. K. Nigam The organic anion transporter family: from physiology to ontogeny and the clinic Am J Physiol Renal Physiol, August 1, 2001; 281(2): F197 - F205. [Abstract] [Full Text] [PDF]
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S. H. Cha, T. Sekine, J.-i. Fukushima, Y. Kanai, Y. Kobayashi, T. Goya, and H. Endou Identification and Characterization of Human Organic Anion Transporter 3 Expressing Predominantly in the Kidney Mol. Pharmacol., April 16, 2001; 59(5): 1277 - 1286. [Abstract] [Full Text]
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P. M. Gerk, C. Y. Oo, E. W. Paxton, J. A. Moscow, and P. J. McNamara Interactions between Cimetidine, Nitrofurantoin, and Probenecid Active Transport into Rat Milk J. Pharmacol. Exp. Ther., January 1, 2001; 296(1): 175 - 180. [Abstract] [Full Text]
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A. Shuprisha, S. H. Wright, and W. H. Dantzler Method for measuring luminal efflux of fluorescent organic compounds in isolated, perfused renal tubules Am J Physiol Renal Physiol, November 1, 2000; 279(5): F960 - F964. [Abstract] [Full Text] [PDF]
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Y. Uwai, H. Saito, Y. Hashimoto, and K.-I. Inui Interaction and Transport of Thiazide Diuretics, Loop Diuretics, and Acetazolamide via Rat Renal Organic Anion Transporter rOAT1 J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 261 - 265. [Abstract] [Full Text]
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S. Wada, M. Tsuda, T. Sekine, S. H. Cha, M. Kimura, Y. Kanai, and H. Endou Rat Multispecific Organic Anion Transporter 1 (rOAT1) Transports Zidovudine, Acyclovir, and Other Antiviral Nucleoside Analogs J. Pharmacol. Exp. Ther., September 1, 2000; 294(3): 844 - 849. [Abstract] [Full Text]
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L. Li, P. J. Meier, and N. Ballatori Oatp2 Mediates Bidirectional Organic Solute Transport: A Role for Intracellular Glutathione Mol. Pharmacol., August 1, 2000; 58(2): 335 - 340. [Abstract] [Full Text]
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R. A. M. H. Van Aubel, R. Masereeuw, and F. G. M. Russel Molecular pharmacology of renal organic anion transporters Am J Physiol Renal Physiol, August 1, 2000; 279(2): F216 - F232. [Abstract] [Full Text] [PDF]
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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]
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A. Pavlova, H. Sakurai, B. Leclercq, D. R. Beier, A. S. L. Yu, and S. K. Nigam Developmentally regulated expression of organic ion transporters NKT (OAT1), OCT1, NLT (OAT2), and Roct Am J Physiol Renal Physiol, April 1, 2000; 278(4): F635 - F643. [Abstract] [Full Text] [PDF]
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G. You, K. Kuze, R. A. Kohanski, K. Amsler, and S. Henderson Regulation of mOAT-mediated Organic Anion Transport by Okadaic Acid and Protein Kinase C in LLC-PK1 Cells J. Biol. Chem., March 31, 2000; 275(14): 10278 - 10284. [Abstract] [Full Text] [PDF]
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H. Uchino, I. Tamai, H. Yabuuchi, K. China, K.-i. Miyamoto, E. Takeda, and A. Tsuji Faropenem Transport across the Renal Epithelial Luminal Membrane via Inorganic Phosphate Transporter Npt1 Antimicrob. Agents Chemother., March 1, 2000; 44(3): 574 - 577. [Abstract] [Full Text]
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S. A. Terlouw, O. Tanriseven, F. G. M. Russel, and R. Masereeuw Metabolite Anion Carriers Mediate the Uptake of the Anionic Drug Fluorescein in Renal Cortical Mitochondria J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 968 - 973. [Abstract] [Full Text]
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E. S. HO, D. C. LIN, D. B. MENDEL, and T. CIHLAR Cytotoxicity of Antiviral Nucleotides Adefovir and Cidofovir Is Induced by the Expression of Human Renal Organic Anion Transporter 1 J. Am. Soc. Nephrol., March 1, 2000; 11(3): 383 - 393. [Abstract] [Full Text] [PDF]
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S. H. Cha, T. Sekine, H. Kusuhara, E. Yu, J. Y. Kim, D. K. Kim, Y. Sugiyama, Y. Kanai, and H. Endou Molecular Cloning and Characterization of Multispecific Organic Anion Transporter 4 Expressed in the Placenta J. Biol. Chem., February 11, 2000; 275(6): 4507 - 4512. [Abstract] [Full Text] [PDF]
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