THE TRANSPORT OF THYROXINE INTO MOUSE NEUROBLASTOMA-CELLS, NB41A3 - THE EFFECT OF L-SYSTEM AMINO-ACIDS

Thyroid hormones must cross the plasma membrane to interact with nuclear or other intracellular receptors. In brain cells, most of the T3 in the nucleus is derived intracellular^ from T4. While a saturable transport system has been demonstrated for T3 in a number of cell types, the evidence for such a system for T4 is less well established. In a mouse neuroblastoma cell line (NB41A3) the transport of T4 was found to be stereospecific, saturable, and energy dependent. When cells were incubated with radiolabeled hormone, theuclear accumulation of l-T4 was 3.8-fold higher than that of d-T4whereas isolated nuclei had a similar Ka for both enantiomers. Exposure of cells to antimycin and monodansylcadaverine decreased nuclear uptake of l-T4 (Ki of 197 and 55 μM, respectively), but had little effect on d-T4 uptake. Furthermore, L-system neutral amino acids, in particular L-phenylalanine at physiological concentrations, were shown to be competitive inhibitors of both T3 and T4 transport. In the presence of 0.1 mM L-phenylalanine the Km of the saturable plasma membrane transport of l-T3 increased 2.3-fold, and that of l-T4 increased 2.1-fold. In contrast, 1.0 mM L-serine or D-phenylalanine had little effect on l-T4 transport. This interaction of L-system amino acid and thyroid hormone transport may be of physiological importance. © 1990 by The Endocrine Society.