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 Pizzagalli, F. Articles by Meier, P. J. Search for Related Content PubMed PubMed Citation Articles by Pizzagalli, F. Articles by Meier, P. J.

Identification of a Novel Human Organic Anion Transporting Polypeptide as a High Affinity Thyroxine Transporter

Division of Clinical Pharmacology and Toxicology (F.P., B.H., B.S., P.J.M.), Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland; Institute of Pathology (U.K.), University of Dresden, D-01307 Dresden, Germany; and Institute of Pharmaceutical Chemistry (G.F.), Department of Applied Biosciences, Swiss Federal Institute of Technology, CH-8092 Zurich, Switzerland

Address all correspondence and requests for reprints to: Prof. P. J. Meier-Abt, Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland. E-mail: meierabt{at}kpt.unizh.ch.

Transport of various amphipathic organic compounds is mediated by organic anion transporting polypeptides (OATPs in humans, Oatps in rodents), which belong to the solute carrier family 21A (SLC21A/Slc21a). Several of these transporters exhibit a broad and overlapping substrate specificity and are expressed in a variety of different tissues. We have isolated and functionally characterized OATP-F (SLC21A14), a novel member of the OATP family. The cDNA (3059 bp) contains an open reading frame of 2136 bp encoding a protein of 712 amino acids. Its gene containing 15 exons is located on chromosome 12p12. OATP-F exhibits 47–48% amino acid identity with OATP-A, OATP-C, and OATP8, the genes of which are clustered on chromosome 12p12. OATP-F is predominantly expressed in multiple brain regions and Leydig cells of the testis. OATP-F mediates high affinity transport of T₄ and reverse T₃ with apparent K_m values of approximately 90 nM and 128 nM, respectively. Substrates less well transported by OATP-F include T₃, bromosulfophthalein, estrone-3-sulfate, and estradiol-17ß-glucuronide. Furthermore, OATP-F-mediated T₄ uptake could be cis-inhibited by L-T₄ and D-T₄, but not by 3,5-diiodothyronine, indicating that T₄ transport is not stereospecific, but that 3',5'-iodination is important for efficient transport by OATP-F. Thus, in contrast to most other family members, OATP-F has a more selective substrate preference and may play an important role in the disposition of thyroid hormones in brain and testis.

This article has been cited by other articles:

				H. Heuer and T. J. Visser Pathophysiological Importance of Thyroid Hormone Transporters Endocrinology, March 1, 2009; 150(3): 1078 - 1083. [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]

				D. E. Westholm, D. D. Stenehjem, J. N. Rumbley, L. R. Drewes, and G. W. Anderson Competitive Inhibition of Organic Anion Transporting Polypeptide 1c1-Mediated Thyroxine Transport by the Fenamate Class of Nonsteroidal Antiinflammatory Drugs Endocrinology, February 1, 2009; 150(2): 1025 - 1032. [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]

				L. M. Roberts, K. Woodford, M. Zhou, D. S. Black, J. E. Haggerty, E. H. Tate, K. K. Grindstaff, W. Mengesha, C. Raman, and N. Zerangue Expression of the Thyroid Hormone Transporters Monocarboxylate Transporter-8 (SLC16A2) and Organic Ion Transporter-14 (SLCO1C1) at the Blood-Brain Barrier Endocrinology, December 1, 2008; 149(12): 6251 - 6261. [Abstract] [Full Text] [PDF]

				A. Mulenga, R. Khumthong, K. C. Chalaire, O. Strey, and P. Teel Molecular and biological characterization of the Amblyomma americanum organic anion transporter polypeptide J. Exp. Biol., November 1, 2008; 211(21): 3401 - 3408. [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]

				E. C. H. Friesema, J. Jansen, J.-w. Jachtenberg, W. E. Visser, M. H. A. Kester, and T. J. Visser Effective Cellular Uptake and Efflux of Thyroid Hormone by Human Monocarboxylate Transporter 10 Mol. Endocrinol., June 1, 2008; 22(6): 1357 - 1369. [Abstract] [Full Text] [PDF]

				J. Jansen, E. C. H. Friesema, M. H. A. Kester, C. E. Schwartz, and T. J. Visser Genotype-Phenotype Relationship in Patients with Mutations in Thyroid Hormone Transporter MCT8 Endocrinology, May 1, 2008; 149(5): 2184 - 2190. [Abstract] [Full Text] [PDF]

				G. Pan, N. Giri, and W. F. Elmquist Abcg2/Bcrp1 Mediates the Polarized Transport of Antiretroviral Nucleosides Abacavir and Zidovudine Drug Metab. Dispos., July 1, 2007; 35(7): 1165 - 1173. [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]

				E. C. H. Friesema, G. G. J. M. Kuiper, J. Jansen, T. J. Visser, and M. H. A. Kester Thyroid Hormone Transport by the Human Monocarboxylate Transporter 8 and Its Rate-Limiting Role in Intracellular Metabolism Mol. Endocrinol., November 1, 2006; 20(11): 2761 - 2772. [Abstract] [Full Text] [PDF]

				A. M. Dumitrescu, X.-H. Liao, R. E. Weiss, K. Millen, and S. Refetoff Tissue-Specific Thyroid Hormone Deprivation and Excess in Monocarboxylate Transporter (Mct) 8-Deficient Mice Endocrinology, September 1, 2006; 147(9): 4036 - 4043. [Abstract] [Full Text] [PDF]

				Y. Sai, Y. Kaneko, S. Ito, K. Mitsuoka, Y. Kato, I. Tamai, P. Artursson, and A. Tsuji PREDOMINANT CONTRIBUTION OF ORGANIC ANION TRANSPORTING POLYPEPTIDE OATP-B (OATP2B1) TO APICAL UPTAKE OF ESTRONE-3-SULFATE BY HUMAN INTESTINAL CACO-2 CELLS Drug Metab. Dispos., August 1, 2006; 34(8): 1423 - 1431. [Abstract] [Full Text] [PDF]

				T. J. Visser The elemental importance of sufficient iodine intake: a trace is not enough. Endocrinology, May 1, 2006; 147(5): 2095 - 2097. [Full Text] [PDF]

				N. Nakao, T. Takagi, M. Iigo, T. Tsukamoto, S. Yasuo, T. Masuda, T. Yanagisawa, S. Ebihara, and T. Yoshimura Possible Involvement of Organic Anion Transporting Polypeptide 1c1 in the Photoperiodic Response of Gonads in Birds Endocrinology, March 1, 2006; 147(3): 1067 - 1073. [Abstract] [Full Text] [PDF]

				J. Bernal The Significance of Thyroid Hormone Transporters in the Brain Endocrinology, April 1, 2005; 146(4): 1698 - 1700. [Full Text] [PDF]

				R. T. Chatterton Jr., A. S. Geiger, E. T. Mateo, I. B. Helenowski, and P. H. Gann Comparison of Hormone Levels in Nipple Aspirate Fluid of Pre- and Postmenopausal Women: Effect of Oral Contraceptives and Hormone Replacement J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1686 - 1691. [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]

				M.M. Ben Saad and D.L. Maurel Reciprocal Interaction Between Seasonal Testis and Thyroid Activity in Zembra Island Wild Rabbits (Oryctolagus cuniculus): Effects of Castration, Thyroidectomy, Temperature, and Photoperiod Biol Reprod, April 1, 2004; 70(4): 1001 - 1009. [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]

				D. Sugiyama, H. Kusuhara, H. Taniguchi, S. Ishikawa, Y. Nozaki, H. Aburatani, and Y. Sugiyama Functional Characterization of Rat Brain-specific Organic Anion Transporter (Oatp14) at the Blood-Brain Barrier: HIGH AFFINITY TRANSPORTER FOR THYROXINE J. Biol. Chem., October 31, 2003; 278(44): 43489 - 43495. [Abstract] [Full Text] [PDF]

				E. C. H. Friesema, S. Ganguly, A. Abdalla, J. E. M. Fox, A. P. Halestrap, and T. J. Visser Identification of Monocarboxylate Transporter 8 as a Specific Thyroid Hormone Transporter J. Biol. Chem., October 10, 2003; 278(41): 40128 - 40135. [Abstract] [Full Text] [PDF]

				N. Mizuno, T. Niwa, Y. Yotsumoto, and Y. Sugiyama Impact of Drug Transporter Studies on Drug Discovery and Development Pharmacol. Rev., September 1, 2003; 55(3): 425 - 461. [Abstract] [Full Text] [PDF]

				F. Pizzagalli, Z. Varga, R. D. Huber, G. Folkers, P. J. Meier, and M. V. St-Pierre Identification of Steroid Sulfate Transport Processes in the Human Mammary Gland J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3902 - 3912. [Abstract] [Full Text] [PDF]

				T. Suzuki, T. Onogawa, N. Asano, H. Mizutamari, T. Mikkaichi, M. Tanemoto, M. Abe, F. Satoh, M. Unno, K. Nunoki, et al. Identification and Characterization of Novel Rat and Human Gonad-Specific Organic Anion Transporters Mol. Endocrinol., July 1, 2003; 17(7): 1203 - 1215. [Abstract] [Full Text] [PDF]