Evaluation of Amino Acid-Mustard Transport as L-Type Amino Acid Transporter 1 (LAT1)-Mediated Alkylating Agents(Biopharmacy)
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概要
- 論文の詳細を見る
The L-type amino acid transporter 1 (LAT1, SLC7A5) is an Na^+ -independent neutral amino acid transporter the expression of which is located in retinal endothelial cells. Due to its broad substrate selectivity, LAT1 has been proposed to mediate the transport of amino acid-related drugs across the blood-tissue barriers. Here, we have investigated the transport screening of amino acid-mustards using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2) which expresses LAT1. We synthesized 5 amino acid-mustards: tyrosine-mustard, phenylglycine-mustard, alanine-mustard, ornithine-mustard, and lysine-mustard. LAT1-medi-ated [^3H]L-phenylalanine (Phe) uptake by TR-iBRB2 cells was inhibited in a competitive manner by tyrosinemustard and phenylglycine-mustard as well as melphalan (phenylalanine-mustard). Phenylglycine-mustard was able to induce the efflux of [^3H]Phe preloaded into the TR-iBRB2 cells expressing LAT1 through the obligatory exchange mechanism, although tyrosine-mustard, alanine-mustard, ornithine-mustard, lysine-mustard, and melphalan did not induce any significant efflux. These findings suggest that phenylglycine-mustard is a better substrate for LAT1 than melphalan and other amino acid-mustards.
- 公益社団法人日本薬学会の論文
- 2008-11-01
著者
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Toyooka Naoki
Organic Chemistry University Of Toyama
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HOSOYA Ken-ichi
Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku
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Tachikawa Masanori
Department Of Pharmaceutics University Of Toyama
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Tachikawa Masanori
Department Of Pharmaceutics Graduate School Of Medicine And Pharmaceutical Sciences University Of To
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Hosoya Ken-ichi
Department Of Molecular Biopharmacy And Genetics Graduate School Of Pharmaceutical Sciences Tohoku U
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Hosoya Ken-ichi
Department Of Pharmaceutics University Of Toyama
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Tomi Masatoshi
Department Of Pharmaceutics University Of Toyama
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Tomi Masatoshi
Department Of Pharmaceutics Graduate School Of Medical And Pharmaceutical Sciences University Of Toy
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KYOKO Hirokazu
Department of Pharmaceutics, University of Toyama
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KATO Atsushi
Hospital Pharmacy, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
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ORIHASHI Masahiro
Teika Pharmaceutical Co., Ltd.
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Kyoko Hirokazu
Department Of Pharmaceutics University Of Toyama
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Orihashi Masahiro
Teika Pharmaceutical Co. Ltd.
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Kato Atsushi
Hospital Pharmacy Graduate School Of Medicine And Pharmaceutical Sciences University Of Toyama
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