GABA TRANSPORTER HETEROGENEITY - PHARMACOLOGY AND CELLULAR-LOCALIZATION

gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitte r In the mammalian brain. GABA is cleared from the synaptic cleft by s pecific, high-affinity, sodium- and chloride-dependent transporters, w hich are thought to be located on presynaptic terminals and surroundin g glial cells. While early studies suggested a distinction between neu ronal and glial GABA transport, molecular cloning has revealed the exi stence of genes for four distinct GABA transporters (termed GAT-1, GAT -2, GAT-3 and BGT-1), thus revealing a greater heterogeneity than prev iously suspected. Heterologous expression has allowed a detailed chara cterization 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 tran sporter has a unique regional distribution in the brain; in conjunctio n with experiments utilizing cell cultures, the neuronal vs glial loca lization of the various transporters is being elucidated. Future studi es 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 age nts for the treatment of neuropsychiatric disorders. Copyright (C) 199 6 Elsevier Science Ltd.