Mechanisms by which human blood platelets accumulate glycine, gaba and amino acid precursors of putative neurotransmitters.

1. We have examined the accumulation by human blood platelets of amino acids that are believed to be involved in neurohumoral transmission in the central nervous system.2. Platelets were incubated in Ca(++)-free Krebs solution at 37 degrees C with radio-active amino acids for various times and then the platelets were analysed for the radioactive substance and its metabolites.3. L-Phenylalanine, L-DOPA, L-tryptophan and L-tyrosine were rapidly accumulated, the equilibrium tissue/medium concentration ratio (C(i)/C(0)) being greater than 10:1 when the concentration of amino acid in the medium was 10(-7)M or lower. Glycine and gamma-aminobutyric acid (GABA) accumulation was less, C(i)/C(0) being lower than 3:1 when C(0) was 10(-7)M.4. Uptake of L-phenylalanine, L-DOPA and L-tryptophan were all decreased or abolished by incubation at 4 degrees C, or with metabolic inhibitors or by disruption of the platelet membrane prior to incubation, while L-tyrosine accumulation was not affected.5. It is considered that L-phenylalanine, L-DOPA and L-tryptophan are accumulated by saturable, energy-dependent processes; that glycine and GABA diffuse into the platelet, and L-tyrosine accumulates as a result of diffusion and intracellular binding.6. None of the amino acids examined showed any significant metabolism during a 20 min incubation. However, some evidence for tyrosine binding to soluble protein was obtained.7. Results are compared to reports of accumulation of these amino acids by the central nervous system.