10 research outputs found
Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs
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