Identification of Thyroid Hormone Transporters

Friesema, Edith C. H.; Docter, R.; Moerings, E. P. C. M.; Stieger, Bruno; Hagenbuch, Bruno; Meier, Peter J.; Krenning, Eric P.; Hennemann, G; Visser, Theo J.

doi:10.1006/bbrc.1998.9974

Cited by 156 publications

(92 citation statements)

References 27 publications

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“…of the present findings with those previously obtained in our laboratory indicate that the rate of transport of T 4 or T 3 by rat MCT8 is at least 10-fold higher than corresponding transport rates with rat NTCP, rat OATP1, and human 4F2/LAT1 (8,24). Transport of T 3 by MCT8 in oocytes is Na ϩ -independent, although T 4 transport is decreased in the absence of Na ϩ .…”

Section: Discussionsupporting

confidence: 77%

“…Among the organic anion transporters, both Na ϩ /taurocholate-cotransporting polypeptide (NTCP) and various members of the Na ϩ -independent organic anion-transporting polypeptide (OATP) family mediate transport of iodothyronines as well as their sulfate and sulfamate derivatives (6,7,24). Recently, a new member, OATP-F, was isolated and characterized (25).…”

Section: Discussionmentioning

confidence: 99%

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Identification of Monocarboxylate Transporter 8 as a Specific Thyroid Hormone Transporter

Friesema

Ganguly

Abdalla

et al. 2003

Journal of Biological Chemistry

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610

415

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Transport of thyroid hormone across the cell membrane is required for its action and metabolism. Recently, a T-type amino acid transporter was cloned which transports aromatic amino acids but not iodothyronines. This transporter belongs to the monocarboxylate transporter (MCT) family and is most homologous with MCT8 (SLC16A2). Therefore, we cloned rat MCT8 and tested it for thyroid hormone transport in Xenopus laevis oocytes. Oocytes were injected with rat MCT8 cRNA, and after 3 days immunofluorescence microscopy demonstrated expression of the protein at the plasma membrane. MCT8 cRNA induced an ϳ10-fold increase in uptake of 10 nM 125 I-labeled thyroxine (T 4 ) Thyroid hormone is important for the development of different tissues and the metabolic function of these tissues throughout life. A well known example is the critical role of thyroid hormone in brain development (1). Transport of thyroid hormone across the cell membrane is required for its metabolism and action. Thyroxine (T 4 ) 1 is the predominant (pro)hormone secreted by the thyroid follicular cells, but 3,3Ј,5-triiodothyronine (T 3 ) is the receptor-active form of thyroid hormone.For its conversion to T 3 , T 4 must enter cells that express the enzymes catalyzing this reaction. The three iodothyronine deiodinases (D1-D3) involved in the activation and inactivation of thyroid hormone are homologous selenoproteins with different catalytic profiles, tissue distributions, and physiological functions (2-4).

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Identification of Monocarboxylate Transporter 8 as a Specific Thyroid Hormone Transporter

Friesema

Ganguly

Abdalla

et al. 2003

Journal of Biological Chemistry

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610

415

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“…Oatp2, on the other hand, has been shown to be unique, so far, in being the only known Oatp that transports the cardiac glycoside digoxin [3]. For Oatp3, unfortunately, the picture is not yet as clear, because it has only been shown to mediate transport of taurocholate and, similar to Oatp1 and Oatp2 [4,31], of the thyroid hormones tri-iodothyronine (' T $ ') and thyroxine (' T % ') [4]. Thus we tested uptake of several of these compounds in OatpcRNA-injected Xenopus lae is oocytes.…”

Section: Resultsmentioning

confidence: 99%

Molecular cloning and functional characterization of the mouse organic-anion-transporting polypeptide 1 (Oatp1) and mapping of the gene to chromosome X

Hagenbuch

Adler²,

Schmid³

1999

Biochemical Journal

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We have cloned a murine member of the organic-anion-transporting polypeptide (Oatp) family of membrane-transport proteins from mouse liver. The cloned cDNA insert of 2783 bp with an open reading frame of 2011 bp codes for a 12-transmembrane 670-amino-acid protein with highest amino acid identity with the rat Oatp1. When expressed in Xenopus laevis oocytes, the mouse Oatp exhibited the same substrate specificity as the rat Oatp1. Besides the common Oatp substrates bromosulphophthalein, taurocholate, oestrone 3-sulphate and ouabain, the new mouse Oatp also mediates transport of the Oatp1-specific magnetic-resonance-imaging agent gadoxetate. The Oatp2-specific cardiac glycoside digoxin, however, is not transported. Kinetic analyses performed for taurocholate and oestrone 3-sulphate revealed apparent Km values of 12 μM and 5 μM respectively. Northern-blot analysis demonstrated a predominant expression in the liver with an additional moderate expression in the kidney. Taken together, the amino acid identity, the functional characteristics and the tissue distribution suggest that we have isolated the murine orthologue of the rat Oatp1, and consequently the identified protein will be called Oatp1. Using fluorescence in situ hybridization, the murine Oatp1 gene was mapped to chromosome XA3-A5.

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“…Further studies investigating the substrate spectrum in more detail have shown that OATP1A2 is capable of transporting a wide range of amphipathic organic anions (Table 1), including bile salts (Kullak-Ublick et al 1995;Meier et al 1997), thyroid hormones (Friesema et al 1999), steroid hormones and their conjugates (Bossuyt et al 1996a), as well as organic cations like N-methylquinidine and others (van Montfoort et al 1999).…”

mentioning

confidence: 99%

Pharmacogenomics of human OATP transporters

König

Seithel

Gradhand

et al. 2006

Naunyn Schmied Arch Pharmacol

316

219

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Organic anion transporting polypeptides (OATPs) mediate the uptake of a broad range of compounds into cells. Substrates for members of the OATP family include bile salts, hormones, and steroid conjugates as well as drugs like the HMG-CoA-reductase inhibitors (statins), cardiac glycosides, anticancer agents like methotrexate, and antibiotics like rifampicin. OATPs are expressed in a variety of different tissues, including intestine, liver, kidney, and brain, suggesting that they play a critical role in drug absorption, distribution, and excretion. The identification and functional characterisation of naturally occurring variations in genes encoding human OATP (SLCO) family members is in the focus of transporter research. As a result of their broad substrate spectrum and their wide tissue distribution, altered transport characteristics or protein localisation can contribute significantly to interindividual variations of drug effects. The analysis of the consequences of genetic variations in genes encoding transport proteins may, therefore, contribute to a better understanding of interindividual differences in drug effects and to individualise treatment regimens with drugs that are substrates for human OATP proteins. In this review, we summarise the current knowledge on genetic variations in transporter genes encoding human OATP family members and their functional consequences analysed by in vitro and in vivo studies.

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Identification of Thyroid Hormone Transporters

Cited by 156 publications

References 27 publications

Identification of Monocarboxylate Transporter 8 as a Specific Thyroid Hormone Transporter

Identification of Monocarboxylate Transporter 8 as a Specific Thyroid Hormone Transporter

Molecular cloning and functional characterization of the mouse organic-anion-transporting polypeptide 1 (Oatp1) and mapping of the gene to chromosome X

Pharmacogenomics of human OATP transporters

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