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

Abstract

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.

Effect of Glutamine Synthetase Inhibition on Brain and Interorgan Ammonia Metabolism in Bile Duct Ligated Rats

“…6 Methionine sulfoximine treatment caused a dramatic increase in percent 15 N-labeling of alanine in brain which must be synthesized de novo via the concerted action by GDH and ALAT (transreamination) since alanine is not transported from blood to brain in rats in measurable amounts. 30 This supports that brain alanine synthesis may be an alternative ammonia-scavenging pathway in BDL rats, confirming the hypothesis based on previous findings in astrocyte-neuron cocultures and healthy rats, especially during inhibition of GS with MSO. [14][15][16] We did not, however, observe an increase in alanine concentration in brain tissue after MSO treatment which is in contrast to what was expected from the study in astrocyte-neuron cocultures.…”

6-[18F]fluoro-l-DOPA Metabolism in Living Human Brain: A Comparison of Six Analytical Methods

“…(Firnau et al ., 1973 ;Garnett et al, 1983;Cumming et al, 1988). FDOPA , the metabolite OMFD, and a num ber of endogenous amino acids are transported from the circulation to brain tissue by an endothelial membrane transporter of large neutral amino acids (Oldendorf and Szabo, 1976) . FDOPA uptake oc curs in all regions of the brain, but retention occurs mainly in the caudate nucleus and putamen (Garnett et aI., 1984).…”

“…A possible ex planation invokes the transport across the blood brain barrier. Both FDOPA and its major metabo lite in plasma, OMFD, are transported from the circulation to brain tissue by the transporter of large neutral amino acids (Wade and Katzman , 1975;Oldendorf and Szabo, 1976). The transporter is nearly saturated and competitors in plasma inhibit the transport of both labeled compounds (Leenders et a!.…”

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

“…VAL, LEU, and ILE levels were analyzed for the purpose of calculating the ratio of plasma TRP, TYR, or PHE, to these other large neutral amino acids (LNAAs). The ratio of precursors to other LNAAs has been suggested to be a more accurate indicator of central precursor depletion than absolute plasma precursor levels, due to the competition between the LNAAs for brain entry via the same AA transporter (Oldendorf and Szabo, 1976).…”