RRC ID 38289
著者 Shikano N, Kotani T, Nakajima S, Ogura M, Nakazawa S, Sagara J, Kobayashi M, Baba T, Yamaguchi N, Kubota N, Kawai K.
タイトル Radioiodinated 4-iodo-L-meta-tyrosine, a system L selective artificial amino acid: molecular design and transport characterization in Chinese hamster ovary cells (CHO-K1 cells).
ジャーナル Nucl Med Biol
Abstract INTRODUCTION:High expression of the system L amino acid transporter has been observed in clinically important tissues including tumors and the blood-brain barrier. We examined amino acid transport system L selectivity of (14)C(U)-L-tyrosine ((14)C-Tyr), (125)I-4-iodo-L-meta-tyrosine (4-(125)I-mTyr), (125)I-6-iodo-L-meta-tyrosine (6-(125)I-mTyr), (125)I-3-iodo-α-methyl-L-tyrosine ((125)I-IMT) and (125)I-3-iodo-L-tyrosine (3-(125)I-Tyr) using Chinese hamster ovary cells (CHO-K1).
METHODS:Cells in the exponential growth phase were incubated with 18.5 kBq of labeled amino acid in 2 mL of phosphate-buffered saline-based uptake solution and an uptake solution with/without Na(+) at 37°C or 4°C. We examined the effects of the following compounds (1.0 mM) on transport: 2-(methylamino)isobutyric acid (a specific inhibitor of system A, in Na(+)-containing uptake solution); 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a specific inhibitor of system L, in Na(+)-free uptake solution); sodium azide and 2,4-dinitrophenol (NaN(3) and DNP, inhibitors of the generation of adenosine triphosphate); p-aminohippurate and tetraethylammonium (PAH and TEA, inhibitors of organic anion and cation transporters); and L- and D-isomers of natural amino acids.
RESULTS:(14)C-Tyr exhibited affinity for systems L, A and ASC. 4-(125)I-mTyr and 3-(125)I-Tyr exhibited high specificity for system L, whereas 6-(125)I-mTyr and (125)I-IMT exhibited affinity for both systems L and ASC. Uptake of 4-(125)I-mTyr was markedly reduced by incubation at 4 °C, and was not significantly inhibited by NaN(3), DNP, PAH or TEA. The inhibition profiles of the L- and D-isomers of natural amino acids indicated that system L mediates the transport of 4-(125)I-mTyr.
CONCLUSIONS:4-(125)I-mTyr exhibited the greatest system L specificity (93.46 ± 0.13%) of all of the tested amino acids.
巻・号 37(8)
ページ 903-10
公開日 2010-11-1
DOI 10.1016/j.nucmedbio.2010.06.006
PII S0969-8051(10)00316-1
PMID 21055620
MeSH Animals Biological Transport / drug effects CHO Cells Cell Proliferation Cricetinae Cricetulus Iodine Radioisotopes Kinetics Monoiodotyrosine / chemistry* Monoiodotyrosine / metabolism* Stereoisomerism Substrate Specificity
IF 2.396
引用数 4
WOS 分野 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
リソース情報
ヒト・動物細胞 CHO-K1