Active transport of gamma-aminobutyric acid and glycine into synaptic vesicles.
Although gamma-aminobutyric acid (GABA) and glycine are recognized as major amino acid inhibitory neurotransmitters in the central nervous system, their storage is poorly understood. In this study we have characterized vesicular GABA and glycine uptakes in the cerebrum and spinal cord, respectively. We present evidence that GABA and glycine are each taken up into isolated synaptic vesicles in an ATP-dependent manner and that the uptake is driven by an electrochemical proton gradient. Uptake for both amino acids exhibited kinetics with low affinity (Km in the millimolar range) similar to vesicular glutamate uptake. The ATP-dependent GABA uptake was not inhibited by the putative amino acid neurotransmitters glycine, taurine, glutamate, or aspartate or by GABA analogs, agonists, and antagonists. Similarly, ATP-dependent glycine uptake was hardly affected by GABA, taurine, glutamate, or aspartate or by glycine analogs or antagonists. The GABA uptake was not affected by chloride, which is in contrast to the uptake of the excitatory neurotransmitter glutamate, whereas the glycine uptake was slightly stimulated by low concentrations of chloride. Tissue distribution studies indicate that the vesicular uptake systems for GABA, glycine, and glutamate are distributed in different proportions in the cerebrum and spinal cord. These results suggest that the vesicular uptake systems for GABA, glycine, and glutamate are distinct from each other.
Kish
P E
PE
Mental Health Research Institute, University of Michigan, Ann Arbor 48109.
Fischer-Bovenkerk
C
C
Ueda
T
T
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism; D013329:Structure-Activity Relationship; D013572:Synaptic Vesicles / Q000378:metabolism*; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002712:Chlorides; D005971:Glutamates; D007476:Ionophores; D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid; D000251:Adenosine Triphosphatases; D005998:Glycine