This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fujiwara, K. Articles by Abe, T. Search for Related Content PubMed PubMed Citation Articles by Fujiwara, K. Articles by Abe, T.

Identification of Thyroid Hormone Transporters in Humans: Different Molecules Are Involved in a Tissue-Specific Manner^1,2

Department of Neurophysiology (K.F., H.A., T.N., M.O., T.S., N.A., M.Se., T.A.), First Department of Surgery (K.F., H.A., M.U., M.O., T.O., K.S., M.Su., S.M.), Department of Pediatrics (T.N., Y.K., K.I.), Second Department of Internal Medicine (T.S., S.I.), Third Department of Internal Medicine (N.A., T.S.), Department of Molecular Pharmacology (K.N.), Tohoku University School of Medicine, Sendai 980-8575, Japan; Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd. (T.T.), Tokyo 140-8710, Japan; and Division of Nephrology, Faculty of Medicine, University of Tokyo (M.T.), Tokyo 113-8655, Japan

Address all correspondence and requests for reprints to: Dr. Takaaki Abe, Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Japan. E-mail: takaabe{at}mail.cc.tohoku.ac.jp

We have recently identified that rat organic anion transporters, polypeptide2 (oatp2) and oatp3, both of which transport thyroid hormones. However, in humans the molecular organization of the organic anion transporters has diverged, and the responsible molecule for thyroid hormone transport has not been clarified, except for human liver-specific transporter (LST-1) identified by us. In this study we isolated and characterized a novel human organic anion transporter, OATP-E from human brain. The isolated complementary DNA encodes a polypeptide of 722 amino acids with 12 transmembrane domains. A rat counterpart, oatp-E, was also identified. Homology analysis and the phylogenetic tree analysis revealed that OATP-E/oatp-E is a subfamily of the organic anion transporter. Human OATP-E transported 3,3',5-triiodo-L-thyronine (K_m, 0.9 µM), thyronine, and rT₃ in a Na⁺-independent manner. Although the clone was isolated from the brain, OATP-E messenger RNA was abundantly expressed in various peripheral tissues. The rat counterpart, oatp-E, also transported 3,3',5-triiodo-L-thyronine. In addition, in this study we revealed that human OATP, which is exclusively expressed in the brain, transported 3,3',5-triiodo-L-thyronine (K_m, 6.5 µM), T₄ (K_m, 8.0 µM), and rT₃. These data suggest that in humans, several different molecules are involved in transporting thyroid hormone: OATP in the brain, LST-1 in the liver, and OATP-E in peripheral tissues.

This article has been cited by other articles:

				T. Minematsu, M. Iwai, K. Sugimoto, N. Shirai, T. Nakahara, T. Usui, and H. Kamimura Carrier-Mediated Uptake of 1-(2-Methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazolium Bromide (YM155 Monobromide), a Novel Small-Molecule Survivin Suppressant, into Human Solid Tumor and Lymphoma Cells Drug Metab. Dispos., March 1, 2009; 37(3): 619 - 628. [Abstract] [Full Text] [PDF]

				S. Leuthold, B. Hagenbuch, N. Mohebbi, C. A. Wagner, P. J. Meier, and B. Stieger Mechanisms of pH-gradient driven transport mediated by organic anion polypeptide transporters Am J Physiol Cell Physiol, March 1, 2009; 296(3): C570 - C582. [Abstract] [Full Text] [PDF]

				M. S. Wagner, S. M. Wajner, and A. L. Maia The role of thyroid hormone in testicular development and function J. Endocrinol., December 1, 2008; 199(3): 351 - 365. [Abstract] [Full Text] [PDF]

				W. M. van der Deure, P. S. Hansen, R. P. Peeters, K. O. Kyvik, E. C. H. Friesema, L. Hegedus, and T. J. Visser Thyroid Hormone Transport and Metabolism by Organic Anion Transporter 1C1 and Consequences of Genetic Variation Endocrinology, October 1, 2008; 149(10): 5307 - 5314. [Abstract] [Full Text] [PDF]

				R. D. Huber, B. Gao, M.-A. Sidler Pfandler, W. Zhang-Fu, S. Leuthold, B. Hagenbuch, G. Folkers, P. J. Meier, and B. Stieger Characterization of two splice variants of human organic anion transporting polypeptide 3A1 isolated from human brain Am J Physiol Cell Physiol, February 1, 2007; 292(2): C795 - C806. [Abstract] [Full Text] [PDF]

				N Shimada and K Yamauchi Characteristics of 3,5,3'-triiodothyronine (T3)-uptake system of tadpole red blood cells: effect of endocrine-disrupting chemicals on cellular T3 response J. Endocrinol., December 1, 2004; 183(3): 627 - 637. [Abstract] [Full Text] [PDF]

				M. V. St-Pierre, T. Stallmach, A. Freimoser Grundschober, J.-F. Dufour, M. A. Serrano, J. J. G. Marin, Y. Sugiyama, and P. J. Meier Temporal expression profiles of organic anion transport proteins in placenta and fetal liver of the rat Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2004; 287(6): R1505 - R1516. [Abstract] [Full Text] [PDF]

				H. Sun, Y. Huang, L. Frassetto, and L. Z. Benet EFFECTS OF UREMIC TOXINS ON HEPATIC UPTAKE AND METABOLISM OF ERYTHROMYCIN Drug Metab. Dispos., November 1, 2004; 32(11): 1239 - 1246. [Abstract] [Full Text] [PDF]

				K. Tohyama, H. Kusuhara, and Y. Sugiyama Involvement of Multispecific Organic Anion Transporter, Oatp14 (Slc21a14), in the Transport of Thyroxine across the Blood-Brain Barrier Endocrinology, September 1, 2004; 145(9): 4384 - 4391. [Abstract] [Full Text] [PDF]

				T. Mikkaichi, T. Suzuki, T. Onogawa, M. Tanemoto, H. Mizutamari, M. Okada, T. Chaki, S. Masuda, T. Tokui, N. Eto, et al. Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney PNAS, March 9, 2004; 101(10): 3569 - 3574. [Abstract] [Full Text] [PDF]

				T. Nozawa, K. Imai, J.-I. Nezu, A. Tsuji, and I. Tamai Functional Characterization of pH-Sensitive Organic Anion Transporting Polypeptide OATP-B in Human J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 438 - 445. [Abstract] [Full Text] [PDF]

				A. Ito, K. Yamaguchi, H. Tomita, T. Suzuki, T. Onogawa, T. Sato, H. Mizutamari, T. Mikkaichi, T. Nishio, T. Suzuki, et al. Distribution of Rat Organic Anion Transporting Polypeptide-E (oatp-E) in the Rat Eye Invest. Ophthalmol. Vis. Sci., November 1, 2003; 44(11): 4877 - 4884. [Abstract] [Full Text] [PDF]

				H. H. A. G. M. van der Putten, E. C. H. Friesema, N. A. Abumrad, M. E. Everts, and T. J. Visser Thyroid Hormone Transport by the Rat Fatty Acid Translocase Endocrinology, April 1, 2003; 144(4): 1315 - 1323. [Abstract] [Full Text] [PDF]

				J. W. A. Ritchie, Y.-B. Shi, Y. Hayashi, F. E. Baird, R. W. Muchekehu, G. R. Christie, and P. M. Taylor A Role for Thyroid Hormone Transporters in Transcriptional Regulation by Thyroid Hormone Receptors Mol. Endocrinol., April 1, 2003; 17(4): 653 - 661. [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]

				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]

				R. P. Peeters, E. C. H. Friesema, R. Docter, G. Hennemann, and T. J. Visser Effects of thyroid state on the expression of hepatic thyroid hormone transporters in rats Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1232 - E1238. [Abstract] [Full Text] [PDF]

				F. Pizzagalli, B. Hagenbuch, B. Stieger, U. Klenk, G. Folkers, and P. J. Meier Identification of a Novel Human Organic Anion Transporting Polypeptide as a High Affinity Thyroxine Transporter Mol. Endocrinol., October 1, 2002; 16(10): 2283 - 2296. [Abstract] [Full Text] [PDF]

				T. Nozawa, M. Nakajima, I. Tamai, K. Noda, J.-i. Nezu, Y. Sai, A. Tsuji, and T. Yokoi Genetic Polymorphisms of Human Organic Anion Transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): Allele Frequencies in the Japanese Population and Functional Analysis J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 804 - 813. [Abstract] [Full Text] [PDF]

				E. C. H. Friesema, R. Docter, E. P. C. M. Moerings, F. Verrey, E. P. Krenning, G. Hennemann, and T. J. Visser Thyroid Hormone Transport by the Heterodimeric Human System L Amino Acid Transporter Endocrinology, October 1, 2001; 142(10): 4339 - 4348. [Abstract] [Full Text] [PDF]

				G. Hennemann, R. Docter, E. C. H. Friesema, M. de Jong, E. P. Krenning, and T. J. Visser Plasma Membrane Transport of Thyroid Hormones and Its Role in Thyroid Hormone Metabolism and Bioavailability Endocr. Rev., August 1, 2001; 22(4): 451 - 476. [Abstract] [Full Text] [PDF]