GABA transporter heterogeneity: pharmacology and cellular localization

Neurochem Int. 1996 Oct;29(4):335-56. doi: 10.1016/0197-0186(95)00158-1.

Abstract

gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain. GABA is cleared from the synaptic cleft by specific, high-affinity, sodium- and chloride-dependent transporters, which are thought to be located on presynaptic terminals and surrounding glial cells. While early studies suggested a distinction between neuronal and glial GABA transport, molecular cloning has revealed the existence of genes for four distinct GABA transporters (termed GAT-1, GAT-2, GAT-3 and BGT-1), thus revealing a greater heterogeneity than previously suspected. Heterologous expression has allowed a detailed characterization of their pharmacological properties, and has revealed that GAT-1 is the site of action of the anticonvulsant drug, Tiagabine. In-situ hybridization and immunocytochemistry demonstrate that each transporter has a unique regional distribution in the brain; in conjunction with experiments utilizing cell cultures, the neuronal vs glial localization of the various transporters is being elucidated. Future studies will be directed at determining the role of each transporter in the regulation of GABAergic transmission, and in the design of additional subtype-specific inhibitors, which may serve as novel therapeutic agents for the treatment of neuropsychiatric disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anisoles / pharmacology
  • Astrocytes / chemistry
  • Carrier Proteins / analysis
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology
  • Carrier Proteins / physiology*
  • GABA Plasma Membrane Transport Proteins
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / pharmacology
  • Membrane Proteins / physiology*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / physiology*
  • Neurons / chemistry
  • Nipecotic Acids / pharmacology
  • Organic Anion Transporters*
  • Subcellular Fractions / chemistry
  • gamma-Aminobutyric Acid / metabolism

Substances

  • 1-(2-(tris(4-methoxyphenyl)methoxy)ethyl)-3-piperidinecarboxylic acid
  • Anisoles
  • Carrier Proteins
  • GABA Plasma Membrane Transport Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Nipecotic Acids
  • Organic Anion Transporters
  • Slc6a1 protein, rat
  • Slc6a13 protein, rat
  • betaine plasma membrane transport proteins
  • gamma-Aminobutyric Acid