文章基本信息

标题：Evaluation of Amino Acid-Mustard Transport as L-Type Amino Acid Transporter 1 (LAT1)-Mediated Alkylating Agents
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作者：Ken-ichi Hosoya ; Hirokazu Kyoko ; Naoki Toyooka 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：11
页码：2126-2130
DOI：10.1248/bpb.31.2126
出版社：The Pharmaceutical Society of Japan
摘要：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-mediated [³H] L -phenylalanine (Phe) uptake by TR-iBRB2 cells was inhibited in a competitive manner by tyrosine-mustard 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.
关键词：L-type amino acid transporter 1;amino acid-mustard;alkylating agent;transport;inner blood–retinal barrier