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Cited by 120Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismCellular transport and secretion

Active transport of gamma-aminobutyric acid and glycine into synaptic vesicles

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Kish, P E, Fischer-Bovenkerk, C, Ueda, T·1989·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.86.10.3877PMC PMC287244
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Abstract

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.

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Authors
Kish, P. E., Fischer-Bovenkerk, C., & Ueda, T.
Affiliations
  • University of Michigan (US)
  • Mental Health Research Institute, University of Michigan, Ann Arbor 48109.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1989-05
Volume
86
Issue
10
Pages
3877-3881
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.86.10.3877
PMC
PMC287244
OpenAlex
W2088408205
Cited by
119
References
35
Citations by year
2026: 2 · 2025: 1 · 2023: 1 · 2022: 3 · 2020: 1 · 2018: 2 · 2017: 1 · 2016: 4 · 2014: 3 · 2013: 1 · 2012: 1
FWCI
4.94
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (5T32MHT5794-07)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
GABA, glycine, synaptic vesicles, vesicular uptake, inhibitory neurotransmitter, ATP-dependent uptake, proton gradient, cerebrum, spinal cord, chloride, amino acid transporters, neurotransmitter storage
MeSH terms
Adenosine Triphosphatases, Animals, Biological Transport, Active, Brain, Chlorides, gamma-Aminobutyric Acid, Glutamates, Glycine, Hydrogen-Ion Concentration, Ionophores, Kinetics, Membrane Potentials, Spinal Cord, Structure-Activity Relationship, Synaptic Vesicles, Tissue Distribution, Neurotransmitter Agents, Rats, In Vitro Techniques

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