Identification of a Novel Human Organic Anion Transporting Polypeptide as a High Affinity Thyroxine Transporter.
Pizzagalli, F; Hagenbuch, B; Stieger, B; Klenk, U; Folkers, G; Meier, P J.
[Article] Molecular Endocrinology. 16(10):2283-2296, October 2002.

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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 Km values of approximately 90 nm and 128 nm, respectively. Substrates less well transported by OATP-F include T3, bromosulfophthalein, estrone-3-sulfate, and estradiol-17[beta]-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.

Copyright (C) 2002 by The Endocrine Society