Inhibitory effects of calcium channel blockers on thyroid hormone uptake in neonatal rat cardiomyocytes
The effects of the Ca2+ channel blockers verapamil, nifedipine, and diltiazem on triiodothyronine (T3) and thyroxine (T4) uptake were tested in cultured cardiomyocytes from 2-day-old rats. Experiments were performed at 37 degrees C in medium with 0.5% BSA for [125I]T3 (100 pM) or 0.1% BSA for [125I]T4 (350 pM). The 15-min uptake of [125I]T3 was 0.124 +/- 0.013 fmol/pM free T3 (n = 6); [125I]T4 uptake was 0.032 +/- 0.003 fmol/pM free T4 (n = 12). Neither T3 nor T4 uptake was affected by 1% DMSO (diluent for nifedipine and verapamil). Uptake of [125I]T3 but not of [125I]T4 was dose dependently reduced by incubation with 1-100 microM verapamil (49-87%, P < 0.05) or nifedipine (53-81%, P < 0.05). The relative decline in [125I]T3 uptake after 4 h of incubation with 10 microM verapamil or nifedipine was less than after 15 min or 1 h, indicating that the major inhibitory effect of the Ca2+ channel blockers occurred at the level of the plasma membrane. The reduction of nuclear [125I]T3 binding by 10 microM verapamil or nifedipine was proportional to the reduction of cellular [125I]T3 uptake. Diltiazem (1-100 microM) had no dose-dependent effect on [125I]T3 uptake but reduced [125I]T4 uptake by 45% (P < 0.05) at each concentration tested. Neither the presence of 20 mM K+ nor the presence of low Ca2+ in the medium affected [125I]T3 uptake. In conclusion, the inhibitory effects of Ca2+ channel blockers on T3 uptake in cardiomyocytes are not secondary to their effects on Ca2+ influx but, rather, reflect interference with the putative T3 carrier in the plasma membrane.
|Adenosine Triphosphate/metabolism, Animals, Animals, Newborn, Biological Transport/drug effects, Calcium Channel Blockers/*pharmacology, Calcium/pharmacology, Cell Membrane/metabolism, Cells, Cultured, Diltiazem/pharmacology, Iodine Radioisotopes/diagnostic use, Muscle Fibers/cytology/drug effects/*metabolism, Myocardium/*cytology, Nifedipine/pharmacology, Potassium/pharmacology, Rats, Rats, Wistar, Research Support, Non-U.S. Gov't, Thyroxine/*pharmacokinetics, Triiodothyronine/*pharmacokinetics, Verapamil/*pharmacology|
|American Journal of Physiology - Heart and Circulatory Physiology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Verhoeven, F.A, Moerings, E.P.C.M, Lamers, J.M.J, Hennemann, G, Visser, T.J, & Everts, M.E. (2001). Inhibitory effects of calcium channel blockers on thyroid hormone uptake in neonatal rat cardiomyocytes. American Journal of Physiology - Heart and Circulatory Physiology. Retrieved from http://hdl.handle.net/1765/9774