The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier

Brain Res. 2000 Oct 6;879(1-2):115-21. doi: 10.1016/s0006-8993(00)02758-x.


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/LAT1 complex participates in L-DOPA transport across the BBB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems
  • Amino Acids / metabolism
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Biological Transport
  • Blood-Brain Barrier*
  • Brain / metabolism*
  • Capillaries / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cerebrovascular Circulation / physiology*
  • Endothelium, Vascular / metabolism*
  • Female
  • Fusion Regulatory Protein-1
  • Levodopa / blood
  • Levodopa / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Protein Subunits
  • Recombinant Proteins / metabolism


  • Amino Acid Transport Systems
  • Amino Acids
  • Antigens, CD
  • Carrier Proteins
  • Fusion Regulatory Protein-1
  • Protein Subunits
  • Recombinant Proteins
  • Levodopa