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.