Amino acid assignment to one of three blood-brain barrier amino acid carriers

1976 ◽  
Vol 230 (1) ◽  
pp. 94-98 ◽  
Author(s):  
WH Oldendorf ◽  
J Szabo
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Blood Brain Barrier ◽  
Internal Standard ◽  
Basic Amino Acid ◽  
Brain Barrier ◽  
Carrier System ◽  
Blood Brain ◽  
Cross Inhibition ◽  
Amino Acid Carrier

The percentages of 22 14C-labeled amino acids remaining in rat brain 15 s after carotid injection were measured relative to a simultaneously injected diffusible internal standard, 3HOH. The injected solution also contained a nondiffusible internal standard, [113mIn]EDTA to correct for incomplete brain blood compartment washout. Self-inhibition and cross-inhibition was demonstrated by inclusion of unlabeled amino acids and carboxylic acids. All amino acids tested, excluding proline, alanine, and glycine, could be assigned to one, and only one, blood-brain barrier carrier system. The neutral carrier system transported phenylalanine, leucine, tyrosine, isoleucine, methionine, tryptophane, valine, DOPA, cysteine, histidine, threonine, glutamine, asparagine, and serine. Affinity for a basic amino acid carrier system was demonstrated for arginine, ornithine, and lysine. A third, low-capacity independent carrier system transporting aspartic and glutamic acids was demonstrated.

scholarly journals Asymmetrical Transport of Amino Acids across the Blood—Brain Barrier in Humans

1990 ◽  
Vol 10 (5) ◽  
pp. 698-706 ◽  
Author(s):  
G. Moos Knudsen ◽  
K. D. Pettigrew ◽  
C. S. Patlak ◽  
M. M. Hertz ◽  
O. B. Paulson
Keyword(s):  
Amino Acids ◽  
Endothelial Cell ◽  
Amino Acid ◽  
Blood Brain Barrier ◽  
Extracellular Fluid ◽  
Brain Barrier ◽  
Reverse Direction ◽  
Single Membrane ◽  
Blood Brain ◽  
The Brain

Blood–brain barrier permeability to four large neutral and one basic amino acid was studied in 30 patients with the double indicator technique. The resultant 64 venous outflow curves were analyzed by means of two models that take tracer backflux and capillary heterogeneity into account. The first model considers the blood–brain barrier as a double membrane where amino acids from plasma enter the endothelial cell. When an endothelial cell volume of 0.001 ml/g was assumed, permeability from the blood into the endothelial cell was, for most amino acids, about 10–20 times larger than the permeability for the reverse direction. The second model assumes that the amino acids, after intracarotid injection, cross a single membrane barrier and enter a well-mixed compartment, the brain extracellular fluid, i.e., the endothelial cell is assumed to behave as a single membrane. With this model, for large neutral amino acids, the permeability out of the extracellular fluid space back to the blood was between 8 to 12 times higher than the permeability from the blood into the brain. Such a difference in permeabilities across the blood–brain barrier can almost entirely be ascribed to the effect of a nonlinear transport system combined with a relatively small brain amino acid metabolism. The significance of the possible presence of an energy-dependent A system at the abluminal side of the blood–brain barrier is discussed and related to the present findings. For both models, calculation of brain extraction by simple peak extraction values underestimates true unidirectional brain uptake by 17–40%. This raises methodological problems when estimating blood to brain transfer of amino acids with this traditional in vivo method.

Na+-dependent transport of large neutral amino acids occurs at the abluminal membrane of the blood-brain barrier

2003 ◽  
Vol 285 (6) ◽  
pp. E1167-E1173 ◽  
Author(s):  
Robyn L. O'Kane ◽  
Richard A. Hawkins
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Blood Brain Barrier ◽  
Basement Membranes ◽  
Brain Barrier ◽  
Large Neutral Amino Acid ◽  
Large Neutral Amino Acids ◽  
Neutral Amino Acids ◽  
Blood Brain ◽  
Dependent Transport

Several Na+-dependent carriers of amino acids exist on the abluminal membrane of the blood-brain barrier (BBB). These Na+-dependent carriers are in a position to transfer amino acids from the extracellular fluid of brain to the endothelial cells and thence to the circulation. To date, carriers have been found that may remove nonessential, nitrogen-rich, or acidic (excitatory) amino acids, all of which may be detrimental to brain function. We describe here Na+-dependent transport of large neutral amino acids across the abluminal membrane of the BBB that cannot be ascribed to currently known systems. Fresh brains, from cows killed for food, were used. Microvessels were isolated, and contaminating fragments of basement membranes, astrocyte fragments, and pericytes were removed. Abluminal-enriched membrane fractions from these microvessels were prepared. Transport was Na+dependent, voltage sensitive, and inhibited by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, a particular inhibitor of the facilitative large neutral amino acid transporter 1 (LAT1) system. The carrier has a high affinity for leucine ( Km21 ± 7 μM) and is inhibited by other neutral amino acids, including glutamine, histidine, methionine, phenylalanine, serine, threonine, tryptophan, and tyrosine. Other established neutral amino acids may enter the brain by way of LAT1-type facilitative transport. The presence of a Na+-dependent carrier on the abluminal membrane capable of removing large neutral amino acids, most of which are essential, from brain indicates a more complex situation that has implications for the control of essential amino acid content of brain.

scholarly journals Brain interstitial fluid glutamine homeostasis is controlled by blood–brain barrier SLC7A5/LAT1 amino acid transporter

2016 ◽  
Vol 36 (11) ◽  
pp. 1929-1941 ◽  
Author(s):  
Elena Dolgodilina ◽  
Stefan Imobersteg ◽  
Endre Laczko ◽  
Tobias Welt ◽  
Francois Verrey ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cerebrospinal Fluid ◽  
Amino Acid ◽  
Blood Brain Barrier ◽  
Interstitial Fluid ◽  
Competitive Inhibition ◽  
Brain Barrier ◽  
Brain Interstitial Fluid ◽  
Blood Brain ◽  
System L

L-glutamine (Gln) is the most abundant amino acid in plasma and cerebrospinal fluid and a precursor for the main central nervous system excitatory (L-glutamate) and inhibitory (γ-aminobutyric acid (GABA)) neurotransmitters. Concentrations of Gln and 13 other brain interstitial fluid amino acids were measured in awake, freely moving mice by hippocampal microdialysis using an extrapolation to zero flow rate method. Interstitial fluid levels for all amino acids including Gln were ∼5–10 times lower than in cerebrospinal fluid. Although the large increase in plasma Gln by intraperitoneal (IP) injection of 15N2-labeled Gln (hGln) did not increase total interstitial fluid Gln, low levels of hGln were detected in microdialysis samples. Competitive inhibition of system A (SLC38A1&2; SNAT1&2) or system L (SLC7A5&8; LAT1&2) transporters in brain by perfusion with α-(methylamino)-isobutyric acid (MeAIB) or 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) respectively, was tested. The data showed a significantly greater increase in interstitial fluid Gln upon BCH than MeAIB treatment. Furthermore, brain BCH perfusion also strongly increased the influx of hGln into interstitial fluid following IP injection consistent with transstimulation of LAT1-mediated transendothelial transport. Taken together, the data support the independent homeostatic regulation of amino acids in interstitial fluid vs. cerebrospinal fluid and the role of the blood–brain barrier expressed SLC7A5/LAT1 as a key interstitial fluid gatekeeper.

Ammonia selectively stimulates neutral amino acid transport across blood-brain barrier

1983 ◽  
Vol 245 (1) ◽  
pp. C74-C77 ◽  
Author(s):  
A. M. Mans ◽  
J. F. Biebuyck ◽  
R. A. Hawkins
Keyword(s):  
Amino Acid ◽  
Blood Brain Barrier ◽  
Monocarboxylic Acid ◽  
Basic Amino Acid ◽  
Neutral Amino Acid ◽  
Brain Barrier ◽  
Transport Systems ◽  
Portacaval Anastomosis ◽  
Portacaval Shunting ◽  
Blood Brain

The response to increased blood NH4+ of three blood-brain barrier transport systems, which are altered after portacaval anastomosis, was studied. NH4+ acetate was infused for 4 or 22 h to raise blood and brain NH4+, and brain glutamine, to levels similar to those observed after portacaval anastomosis. While brain glutamine content was much higher (16–20 mumol/g) than normal (6 mumol/g) at both times, the permeability of the blood-brain barrier to the neutral amino acid [14C]tryptophan was greater only after 22 h of infusion. After discontinuing the infusion for 5 h, tryptophan transport returned to normal, whereas brain glutamine remained elevated (13 mumol/g). Thus there seemed to be no relationship between the rate of transport and glutamine content. The permeability to [14C]sucrose was unaltered, showing that the integrity of the blood-brain barrier was maintained. Other changes that are characteristic of portacaval shunting, such as decreased basic amino acid ([14C]lysine) and monocarboxylic acid (3-[14C]hydroxybutyrate) transport, were not reproduced by 22 h of infusion. The results demonstrated that the continued presence of NH4+ could be responsible for the change in at least one of the transport systems that are affected by portacaval shunting.

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