| Evaluation of amino acid-mustard transport as L-type amino acid transporter 1 (LAT1)-mediated alkylating agents. | |
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MedLine Citation:
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PMID: 18981585 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ken-Ichi Hosoya; Hirokazu Kyoko; Naoki Toyooka; Atsushi Kato; Masahiro Orihashi; Masatoshi Tomi; Masanori Tachikawa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biological & pharmaceutical bulletin Volume: 31 ISSN: 0918-6158 ISO Abbreviation: Biol. Pharm. Bull. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-04 Completed Date: 2009-01-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9311984 Medline TA: Biol Pharm Bull Country: Japan |
Other Details:
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Languages: eng Pagination: 2126-30 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutics, University of Toyama, Toyama, Japan. hosoyak@pha.u-toyama.ac.jp |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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metabolism,
pharmacokinetics*,
pharmacology Animals Biological Transport Cell Line Dose-Response Relationship, Drug Endothelial Cells / drug effects, metabolism Large Neutral Amino Acid-Transporter 1 / metabolism* Mustard Compounds / metabolism, pharmacokinetics* Protein Binding Rats Retina / cytology, drug effects, metabolism Substrate Specificity Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Large Neutral Amino Acid-Transporter 1; 0/Mustard Compounds |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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