RELATIONSHIP BETWEEN THYROID-HORMONE TRANSPORT AND NEUTRAL AMINO-ACID-TRANSPORT IN JAR HUMAN CHORIOCARCINOMA CELLS

The relationship between the transport of the thyroid hormone T-3 and the transport of neutral amino acids was investigated in JAR human placental choriocarcinoma cells. The uptake of leucine, mediated by the amino acid transport system L, was inhibited by T-3 and T-4, and the nature of inhibition was competitive. Uptake of T-3 into the cells was predominantly Na+ independent, and so was that of leucine. However, although an acidic extracellular pH stimulated leucine uptake, the uptake of T-3 remained unaffected. In addition, leucine failed to inhibit T-3 uptake. The aromatic amino acids phenylalanine and tryptophan were found to inhibit the uptake of T-3, but these two amino acids were transported into the cells predominantly via system L. The amino acid transport system T, which is specific for aromatic amino acids, was not detectable in these cells. Treatment of the cells with the calmodulin antagonist CGS 9343 B stimulated the uptake of leucine and tryptophan, but inhibited the uptake of T-3. Kinetic analysis of T-3 uptake revealed the presence of a single saturable system for this hormone in these cells, and the Michaelis-Menten constant for this system was 0.77 +/- 0.06 mu M. Metabolic poisons that interfere with the cellular generation of ATP had no effect on the uptake of T-3 It is concluded that in placental choriocarcinoma cells, 1) T-3 and T-4 are high affinity competitive inhibitors of the amino acid transport system L, 2) uptake of T-3 occurs via a specific Na+-independent, energy-independent, and saturable mechanism that is unrelated to the amino acid transport systems L and T, 3) the aromatic amino acids phenylalanine and tryptophan interact, although weakly, with the T-3 uptake system, and 4) calmodulin-dependent processes participate in the regulation of the T-3 uptake system.