Molecular and functional identification of large neutral amino acid transporters LAT1 and LAT2 and their pharmacological relevance at the blood‐brain barrier

@article{Kido2001MolecularAF,
  title={Molecular and functional identification of large neutral amino acid transporters LAT1 and LAT2 and their pharmacological relevance at the blood‐brain barrier},
  author={Yasuto Kido and Ikumi Tamai and Hiroshi Uchino and F Suzuki and Yoshimichi Sai and Akira Tsuji},
  journal={Journal of Pharmacy and Pharmacology},
  year={2001},
  volume={53}
}
We present here the evidence of molecular and functional expression of LAT1 and LAT2, subunits of the large neutral amino acid transporter system L, in cultured brain capillary endothelial cells of the rat. By means of the RT‐PCR method, transcripts of LAT1, LAT2 and heavy chain of 4F2 antigen (4F2hc) were detected in rat primary cultured brain capillary endothelial cells (BCECs) and immortalized subline, RBEC1. The uptake properties of RBEC1, such as [3H]leucine and l‐[3H]DOPA uptake, were… Expand
Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2.
  • E. D. del Amo, A. Urtti, M. Yliperttula
  • Chemistry, Medicine
  • European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2008
TLDR
The current functional knowledge on LAT1 and LAT2 is presented with emphasis on their potential involvement in pharmacokinetics, and cross-linked heterodimers of light chain with different heavy chains are presented. Expand
Establishment of Stable Cell Lines With High Expression of Heterodimers of Human 4F2hc and Human Amino Acid Transporter LAT1 or LAT2 and Delineation of Their Differential Interaction With α-Alkyl Moieties
TLDR
It is demonstrated that α-alkyl groups interfere with the interaction with LAT2, and these cell lines with higher practical advantages would be useful for screening and analyzing compounds to develop LAT1-specific drugs that can be used for cancer diagnosis and therapeutics. Expand
Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line
TLDR
The results indicate that LAT1, but not LAT2, recognizes pregabalin as a substrate, and it is suggested that LAT 1 mediates pre gabalin transport at the BBB. Expand
Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1).
TLDR
Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents and the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Expand
Endotoxin-induced inflammation down-regulates l-type amino acid transporter 1 (LAT1) expression at the blood–brain barrier of male rats and mice
TLDR
LPS-induced inflammation rapidly decreases LAT1 mRNA expression at the blood–brain barrier in a very similar manner to primary thyroid hormone transporters, while changes in LAT1 protein level follow a slower kinetics, raising the possibility that inflammation may similarly down-regulate other blood– brain barrier transport systems at the transcriptional level. Expand
Characterization and astrocytic modulation of system L transporters in brain microvasculature endothelial cells
TLDR
It is proposed that system L functions as influx and/or efflux transport machinery displaying a greater propensity for the outward transport of large and small neutral amino acids (NAAs) transporters, that is, LAT1/4F2hc and LAT2/ 4F2Hc, respectively. Expand
Transport of Iodothyronines by Human L-Type Amino Acid Transporters.
TLDR
It is suggested that different sets of transporters with specific influx or efflux capacities may cooperate to regulate the cellular thyroid state. Expand
LAT1 activity of carboxylic acid bioisosteres: Evaluation of hydroxamic acids as substrates.
TLDR
The results lend support to a recent account that amino acid esters are LAT1 substrates, and that hydrogen bonding may be as important as charge for interaction with the transporter binding site. Expand
Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2.
TLDR
A major molecular mechanism by which MeHg is transported across cell membranes is described and metal complexes may form a novel class of substrates for amino acid carriers, indicating that these transport proteins may participate in metal ion homoeostasis and toxicity. Expand
The Effects of Prodrug Size and a Carbonyl Linker on l‐Type Amino Acid Transporter 1‐Targeted Cellular and Brain Uptake
TLDR
It is found that esters of meta‐carboxyl l‐phenylalanine had better LAT1 transport rates than the corresponding acylated l‐tyrosine analogues, however, as the size of the hydrophobic moiety increased, there was a decrease in LAT1 Transport rate with a concomitant increase in potency of inhibition. Expand
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TLDR
In in vitro translation, LAT1 was shown to be a nonglycosylated membrane protein consistent with the property of 4F2 light chain, suggesting LAT1 is at least one of the proteins formerly referred to as 4F 2 light chain. Expand
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TLDR
These studies show that the LAT1 transcript is selectively expressed at the BBB compared with other tissues, and the abundance of the LAT 1 mRNA at theBBB is manyfold higher than that of transcripts such as the 4F2hc antigen, actin, or the Glut1 glucose transporter. Expand
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TLDR
A cDNA from rat small intestine is isolated that encodes a novel Na+-independent neutral amino acid transporter with distinctive characteristics in substrate selectivity and transport property, and it is suggested that the heterodimeric complex of LAT-2 and 4F2 heavy chain is involved in the trans-cellular transport of neutral amino acids in epithelia and blood-tissue barriers. Expand
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Introduction Amino acids serve critical roles in brain and are required for normal brain development and function. However, marked differences exist among amino acids, in the roles they serve andExpand
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