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 intracellularly 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, the nuclear accumulation of L-T4 was 3.8-fold higher than that of D-T4, whereas 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 microM, 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.
Lakshmanan
M
M
Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Goncalves
E
E
Lessly
G
G
Foti
D
D
Robbins
J
J
D000596:Amino Acids / Q000494:pharmacology*; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D001667:Binding, Competitive; D001693:Biological Transport, Active / Q000187:drug effects; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D003515:Cycloleucine / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D010649:Phenylalanine / Q000494:pharmacology; D013237:Stereoisomerism; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D014284:Triiodothyronine; D003515:Cycloleucine; C032456:antimycin; C100049:2-aminoisobutyric acid; D010649:Phenylalanine; D000968:Antimycin A; C008542:monodansylcadaverine; D002103:Cadaverine; D013974:Thyroxine