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Titolo:
The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier
Autore:
Kageyama, T; Nakamura, M; Matsuo, A; Yamasaki, Y; Takakura, Y; Hashida, M; Kanai, Y; Naito, M; Tsuruo, T; Minato, N; Shimohama, S;
Indirizzi:
Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, Kyoto 6068507, Japan Kyoto Univ Kyoto Japan 6068507 pt Neurol, Sakyo Ku, Kyoto 6068507, Japan Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Drug Delivery Res, Kyoto, Japan Kyoto Univ Kyoto Japan maceut Sci, Dept Drug Delivery Res, Kyoto, Japan Kyorin Univ, Sch Med, Dept Pharmacol & Toxicol, Tokyo, Japan Kyorin Univ Tokyo Japan Sch Med, Dept Pharmacol & Toxicol, Tokyo, Japan Japan Sci & Technol Corp, PRESTO, Tokyo, Japan Japan Sci & Technol Corp Tokyo Japan Technol Corp, PRESTO, Tokyo, Japan Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan Univ Tokyo Tokyo Japan Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan Kyoto Univ, Grad Sch Med, Dept Immunol & Cell Biol, Kyoto, Japan Kyoto Univ Kyoto Japan Sch Med, Dept Immunol & Cell Biol, Kyoto, Japan
Titolo Testata:
BRAIN RESEARCH
fascicolo: 1-2, volume: 879, anno: 2000,
pagine: 115 - 121
SICI:
0006-8993(20001006)879:1-2<115:T4CTLA>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINO-ACID-TRANSPORT; 4F2 HEAVY-CHAIN; ENDOTHELIAL-CELLS; PARKINSONS-DISEASE; HUMAN ERYTHROCYTES; BROAD-SPECIFICITY; MEMBRANE-PROTEIN; P-GLYCOPROTEIN; EXPRESSION; SYSTEM;
Keywords:
L-DOPA; blood-brain barrier; system L; 4F2hc; LAT1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Shimohama, S Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, 54 Shogoin Kawaharacho, Kyoto 6068507, Japan Kyoto Univ 54 Shogoin Kawaharacho Kyoto Japan 6068507 Japan
Citazione:
T. Kageyama et al., "The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier", BRAIN RES, 879(1-2), 2000, pp. 115-121

Abstract

L-DOPA is transported across the blood-brain barrier (BBB) by an amino acid transporter, system L. Recently, it has been demonstrated that system L consists of two subunits, 4F2hc and either LAT1 or LAT2. 4F2hc/LAT1 and 4F2hc/LAT2 show different transport characteristics, while their distribution in the brain has not been determined. To clarify whether 4F2hc/LAT1 participates in L-DOPA transport across the BBB, we first examined the expression of 4F2hc/LAT1 in the mouse brain capillary endothelial cell line, MBEC4, as an in vitro BBB model. Northern hybridization and immunoblotting revealed that both 4F2hc and LAT1 are expressed and form a heterodimer in MBEC4 cells. To confirm whether 4F2hc/LAT1 acts as system L to transport L-DOPA, we characterized L-DOPA uptake into the cells. The uptake process was time-dependent, temperature-sensitive, and Na+-independent. Neutral amino acids with bulky side chains and a bicyclic amino acid, 2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid (BCH), inhibited L-DOPA uptake into MBEC4 cells to a great extent, while an acidic amino acid, basic amino acids, and glycine had no effect. Other neutral amino acids, such as alanine, asparagine, glutamine, serine, and threonine inhibited L-DOPA uptake by 40-70% at most. These characteristics are more compatible with those of 4F2hc/LAT1, rather than those of 4F2hc/LAT2. Finally, immunohistochemistry;with anti-LAT1 antibody demonstrated that LAT1 is predominantly expressed in the microvessels of the central nervous system. This is the first report showing that the 4F2hc/LAT1complex participates in L-DOPA transport across the BBB. (C) 2000 ElsevierScience B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/21 alle ore 07:40:37