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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
The activity of GABA-transporters located predominantly upon neurones (GAT-1), glia (GAT-3) or both (GAT-2, BGT-1) serves to terminate phasic GABA-ergic transmission, maintain low ambient extracellular concentrations of GABA, and recycle GABA for reuse by neurones. Nonetheless, ambient concentrations of GABA are sufficient to sustain tonic inhibition mediated by high affinity GABAA receptors in certain neuronal populations [18]. GAT1 is the predominant GABA transporter in the brain and occurs primarily upon the terminals of presynaptic neurones and to a much lesser extent upon distal astocytic processes that are in proximity to axons terminals. GAT3 resides predominantly on distal astrocytic terminals that are close to the GABAergic synapse. By contrast, BGT1 occupies an extrasynaptic location possibly along with GAT2 which has limited expression in the brain [15]. TauT is a high affinity taurine transporter involved in osmotic balance that occurs in the brain and non-neuronal tissues, such as the kidney, brush border membrane of the intestine and blood brain barrier [4,12]. CT1, which transports creatine, has a ubiquitous expression pattern, often co-localizing with creatine kinase [4].
GAT1 / SLC6A1
C
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GAT2 / SLC6A13 C Show summary » |
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GAT3 / SLC6A11 C Show summary » |
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BGT1 / SLC6A12 C Show summary »
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TauT / SLC6A6 C Show summary » |
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CT1 / SLC6A8 C Show summary » |
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Transporters. Br J Pharmacol. 180 Suppl 2:S374-469.
The IC50 values for GAT1-4 reported in the table reflect the range reported in the literature from studies of both human and mouse transporters. There is a tendency towards lower IC50 values for the human orthologue [14]. SNAP-5114 is only weakly selective for GAT 2 and GAT3, with IC50 values in the range 22 to >30 µM at GAT1 and BGT1, whereas NNC052090 has at least an order of magnitude selectivity for BGT1 [see [5,17] for reviews]. Compound (R)-4d [PMID: 16766089] is a recently described compound that displays 20-fold selectivity for GAT3 over GAT1 [11]. In addition to the inhibitors listed, deramciclane is a moderately potent, though non-selective, inhibitor of all cloned GABA transporters (IC50 = 26-46 µM; [8]). Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine that potently inhibit the uptake of [3H]GABA into rat synaptosomes have been described [13]. Several derivatives of exo-THPO (e.g. N-methyl-exo-THPO and N-acetyloxyethyl-exo-THPO) demonstrate selectivity as blockers of astroglial, versus neuronal, uptake of GABA [see [5,16] for reviews]. GAT3 is inhibited by physiologically relevant concentrations of Zn2+ [6]. Taut transports GABA, but with low affinity, but CT1 does not, although it can be engineered to do so by mutagenesis guided by LeuT as a structural template [10]. Although inhibitors of creatine transport by CT1 (e.g. β-guanidinopropionic acid, cyclocreatine, guanidinoethane sulfonic acid) are known (e.g. [7]) they insufficiently characterized to be included in the table.