Neuron

Neuron

Volume 9, Issue 2, August 1992, Pages 337-348
Journal home page for Neuron

Article
Functional expression and CNS distribution of a β-alanine-sensitive neuronal GABA transporter

https://doi.org/10.1016/0896-6273(92)90172-AGet rights and content

Abstract

The synaptic action of γ-aminobutyric acid (GABA) is terminated by high affinity, Na+-dependent transport processes in both neurons and glia. We have isolated a novel GABA transporter cDNA, GAT-B, which encodes a high affinity (Km = 2.3 μM), Na+- and Cl−-dependent GABA transport protein that is potently blocked by β-alanine, a compound generally considered a selective inhibitor of glial transport. However, in situ hybridization studies indicate that GAT-B mRNA is expressed predominantly within neurons. These data indicate that the neuronal-glial distinction of GABA transporters based on inhibitor sensitivities must be reconsidered and suggest a greater diversity of GABA transporters than has been predicted by previous pharmacologic studies.

References (63)

  • P. Krogsgaard-Larsen et al.

    GABA uptake inhibitors: relevance to antiepileptic drug research

    Epilepsy Res.

    (1987)
  • J. Kyte et al.

    A simple method for displaying the hydropathic character of a protein

    J. Mol. Biol.

    (1982)
  • O.M. Larsson et al.

    Differences in uptake kinetics of cis-3-aminocyclohexane carboxylic acid into neurons and astrocytes in primary cultures

    Brain Res.

    (1983)
  • G. Levi et al.

    Enrichment of differentiated, stellate astrocytes in cerebellar interneuron cultures as studied by GFAP immunofluorescence and auto radiographic uptake patterns with [3H]d-aspartate and [3H]GABA

    Dev. Brain Res.

    (1983)
  • D.L. Martin et al.

    High affinity transport of taurine and β-alanine and low affinity transport of γ-aminobutyric acid by a single transport system in cultured glioma cells

    J. Biol. Chem.

    (1979)
  • B.S. Meldrum

    Epilepsy and γ-aminobutyric acid-mediated inhibition

    Int. Rev. Neurobiol.

    (1975)
  • R.C. Ogden et al.

    Electrophoresis in agarose and acrylamide gels

    Meth. Enzymol.

    (1987)
  • G. Reynolds et al.

    Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia

    Biol. Psychiatry

    (1990)
  • R. Reynolds et al.

    Selective uptake of neuroactive amino acids by both oligodendrocytes and astrocytes in primary dissociated cell culture: a possible role for oligo-dendrocytes in neurotransmitter metabolism

    Brain Res.

    (1986)
  • D.E. Rhoads et al.

    Stimulation of synaptosomal uptake of neurotransmitter amino acids by insulin: possible role of insulin as a neuromodulator

    Biochem. Biophys. Res. Commun.

    (1984)
  • F. Schon et al.

    The characterisation of [3H]GABA uptake into the satellite glial cells of rat sensory ganglia

    Brain Res.

    (1974)
  • F. Schon et al.

    Selective uptake of [3H]β-alanine by glia: association with the glial uptake system for GABA

    Brain Res.

    (1975)
  • B.K. Schrier et al.

    On the role of glial cells in the mammalian nervous system

    J. Biol. Chem.

    (1974)
  • G.P. Wilkin et al.

    Cerebellar astroglial cells in primary culture: expression of different morphological appearances and different ability to take up [3H]d-aspartate and [3H]GABA

    Dev. Brain Res.

    (1983)
  • A. Yamauchi et al.

    Cloning of a Na+-and CI− -dependent betaine transporter that is regulated by hypertonicity

    J. Biol. Chem.

    (1992)
  • V.J. Balcar et al.

    High affinity uptake of γ-aminobutyric acid in cultured glial and neuronal cells

    Neurochem. Res.

    (1979)
  • F.M. Benes et al.

    Deficits in small interneurons in prefrontal and cingulate cortex of schizophrenic and schizoaffective patients

    Arch. Gen. Psychiatry

    (1991)
  • F.M. Benes et al.

    Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics

    J. Neurosci.

    (1992)
  • R.D. Blakely et al.

    Cloning and expression of a functional serotonin transporter from rat brain

    Nature

    (1991)
  • R.D. Blakely et al.

    Distinct, developmentally regulated brain mRNAs direct the synthesis of neurotransmitter transporters

    J. Neurochem.

    (1991)
  • G. Bonnano et al.

    A carrier for GABA uptake exists on noradrenaline nerve endings in selective rat brain areas but not on serotonin terminals

    J. Neural. Transm.

    (1987)

    • Cited by (0)

    View full text
    Copyright © 1992