Inhibition of gamma-aminobutyrate and glycine uptake into synaptic vesicles.
The substrate specificity of vesicular GABA and glycine uptake was studied in vesicle fractions from brain and spinal cord, respectively. Glycine, beta-alanine and gamma-vinyl-GABA were competitive inhibitors of the GABA uptake were competitive inhibitors of the GABA uptake by synaptic vesicles in brain. Likewise GABA and beta-alanine turned out to be competitive inhibitors of vesicular uptake of glycine in spinal cord. The apparent K1 values were in the same range as the respective Km values for the transport systems. Accumulation of different amino acids were examined, and the structurally related amino acids GABA, beta-alanine and glycine were all taken up by both vesicle fractions. In the present study, we suggest that there are similarities in the vesicular transporters for GABA and glycine, and the two amino acids are probably taken up into the same vesicle population. The key factor in differentiating between GABA and glycine as transmitters in the terminals could be the synthesis and the high-affinity synaptosomal uptake.
Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller.
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Christensen
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Fykse
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D000409:Alanine / Q000493:pharmacokinetics; D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D005998:Glycine / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism; D013379:Substrate Specificity; D013572:Synaptic Vesicles / Q000378:metabolism*; D013654:Taurine / Q000493:pharmacokinetics; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics*
D013654:Taurine; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D000409:Alanine; D005998:Glycine