title: Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs.
abstract: Cellular and nuclear uptake of [125I]tri-iodothyronine (T3) and [125I]triiodothyroacetic acid (Triac) were compared in cardiomyocytes of 2-3 day old rats, and the effect of thyroid hormone analogs on cellular T(3) uptake was measured. Cells (5-10 x 10(5) per well) were cultured in DMEM-M199 with 5% horse serum and 5% FCS. Incubations were performed for from 15 min to 24 h at 37 degrees C in the same medium, 0.5% BSA and [125I]T3 (100 pM), or [125I]Triac (240 pM). Expressed as % dose, T(3) uptake was five times Triac uptake, but expressed as fmol/pM free hormone, Triac uptake was at least 30% (P<0.001) greater than T3 uptake, whereas the relative nuclear binding of the two tracers was comparable. The 15 min uptake of [125I]T3 was competitively inhibited by 10 microM unlabeled T3 (45-52%; P<0.001) or 3,3'- diiodothyronine (T2) (52%; P<0.001), and to a smaller extent by thyroxine (T(4)) (27%; 0.05<P<0.1). In contrast, 10 microM 3,5-T2, Triac, or tetraiodothyroacetic acid (Tetrac) did not affect T3 uptake after 15 min or after 24 h. Diiodothyropropionic acid (DITPA) (10 microM) reduced 15-min T3 uptake by about 24% (P<0.05), but it had a greater effect after 4 h (56%; P<0.001). Exposure to 10 nM DITPA during culture reduced cellular T3 uptake, as did 10 nM T3, suggesting down-regulation of the plasma membrane T3 transporters. We conclude that i) Triac is taken up by cardiomyocytes; ii) 3,3'-T2 and, to a lesser extent, DITPA and T4 interfere with plasma membrane transport of T3, whereas 3,5-T2, Triac, or Tetrac do not; iii) the transport mechanism for Triac is probably different from that for T3.
authors: Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.
authors: F A
authors: FA
authors: Verhoeven
authors: H H A G M
authors: HH
authors: Van der Putten
authors: G
authors: G
authors: Hennemann
authors: J M J
authors: JM
authors: Lamers
authors: T J
authors: TJ
authors: Visser
authors: M E
authors: ME
authors: Everts
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003650:Decamethonium Compounds; D004104:Diiodothyronines / Q000494:pharmacology; D005260:Female; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D003650:Decamethonium Compounds; D004104:Diiodothyronines; D007457:Iodine Radioisotopes; D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; C030629:3,3'-diiodothyronine; C033019:decamethonium; C011126:tetraiodothyroacetic acid; D013974:Thyroxine