GABA Transporters

GABA transporters are sodium- and chloride-dependent members of the solute carrier family 6 (SLC6) that mediate the rapid removal of GABA and maintain low extracellular levels. Four 12-TM domain transporters have been identified and localized to neurons and glia.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
0206 β-Alanine
GABA uptake inhibitor (GAT-2 and -3); also glycine receptor agonist and MRGPRD agonist
1296 CI 966 hydrochloride
Selective inhibitor of GAT-1
0234 Guvacine hydrochloride
Specific GABA uptake inhibitor
2747 NNC 05-2090 hydrochloride
GABA uptake inhibitor; moderately BGT-1 selective
1779 NNC 711
Selective GAT-1 inhibitor
0768 Riluzole hydrochloride
GABA uptake inhibitor; also inhibits glutamate release and blocks NaV channels
1081 SKF 89976A hydrochloride
Potent GAT-1 inhibitor; brain penetrant
1561 (S)-SNAP 5114
GABA uptake inhibitor
0181 TACA
GABA uptake inhibitor; also GABAA agonist and substrate for GABA-T
4256 Tiagabine hydrochloride
Selective GAT-1 inhibitor; anticonvulsant

GABA transporters are sodium- and chloride-dependent members of the solute carrier family 6 (SLC6) that mediate the rapid removal of GABA and maintain low extracellular levels. Four 12-TM domain transporters (GAT-1, GAT-2, GAT-3 and BGT-1) have been identified and localized to neurons and glia.

While GAT-1, GAT-2, GAT-3 and BGT-1 bind GABA with varying affinities, they share structural motifs including 12-TM domains, extracellular glycosylation sites and intracellular consensus sites for phosphorylation. A vesicular transporter (VGAT) has also been identified. This member of the SCL32 family is both structurally and functionally distinct, containing 10-TM domains and being found in GABAergic and glycinergic neurons.

Some anticonvulsants have been reported to act upon the GABA transporters. There is evidence to suggest that GABA transporters are linked to epilepsy, affective disorders and schizophrenia.

External sources of pharmacological information for GABA Transporters :

    Literature for GABA Transporters

    Tocris offers the following scientific literature for GABA Transporters to showcase our products. We invite you to request* or download your copy today!

    *Please note that Tocris will only send literature to established scientific business / institute addresses.


    Pain

    Pain Research Product Guide

    A collection of over 250 products for pain research, the guide includes research tools for the study of:

    • Nociception
    • Ion Channels
    • G-Protein-Coupled Receptors
    • Intracellular Signaling
    GABA Receptors

    GABA Receptors Scientific Review

    Written by Ian Martin, Norman Bowery and Susan Dunn, this review provides a history of the GABA receptor, as well as discussing the structure and function of the various subtypes and the clinical potential of receptor modulators; compounds available from Tocris are listed.

    Addiction

    Addiction Poster

    The key feature of drug addiction is the inability to stop using a drug despite clear evidence of harm. This poster describes the brain circuits associated with addiction, and provides an overview of the main classes of addictive drugs and the neurotransmitter systems that they target.

    Epilepsy

    Epilepsy Poster

    Epilepsy is a brain disease that affects 60 million people globally. More than 20 anti-seizure drugs are currently available, but these do not address the underlying causes of the condition. This poster summarizes current knowledge about the development of the condition and highlights some approaches that have disease-modifying effects in proof-of-concept studies.

    Schizophrenia

    Schizophrenia Poster

    Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster describes the neurobiology of Schizophrenia, as well as highlighting the genetic and environmental factors that play a fundamental role in the etiology of the disease. The current and emerging drug targets are also discussed.

    GABA Transporter Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    GAT-1 Human SLC6A1 NM_003042 P30531
    Mouse Slc6a1 NM_178703 P31648
    Rat Slc6a1 NM_024371 P23978
    GAT-2 Human SLC6A13 NM_016615 Q9NSD5
    Mouse Slc6a12 NM_133661 P31651
    Rat Slc6a13 NM_133623 P31646
    GAT-3 Human SLC6A11 NM_014229 P48066
    Mouse Slc6a13 NM_144512 P31649
    Rat Slc6a11 NM_024372 P31647
    BGT-1 Human SLC6A12 NM_003044 P48065
    Rat Slc6a12 NM_017335 P48056
    VGAT Human SLC32A1 NM_080552 Q9H598
    Mouse Slc32a1 NM_009508 O35633
    Rat Slc32a1 NM_031782 O35458

    Properties of GABA Transporters

    Transporter GAT-1 GAT-2 GAT-3 BGT-1
    Tissue Localization1 Mainly neuronal cells in CNS Epithelial, glial and neuronal cells (mainly CNS) Mainly glial cells in CNS and retina Probably mainly glial cells in CNS and kidney
    Selected Inhibitors IC50 (μM)
    β-Alanine (0206) 56902 192 582 13202
    CI 966 (1296) 0.262 2972 3332 3002
    Guvacine (0234) 142 582 1192 18702
    (±)-Nipecotic acid (0236) 82 382 1062 23702
    NNC 711 (1779) 0.042 1712 17002 6222
    SKF 89976A (1081) 0.132 5502 9442 72102
    (S)-SNAP 5114 (1561) 3883 213 53 1403

    IC50 values are for inhibition of [3H]-GABA uptake by cloned human GAT-1, rat GAT-2, human GAT-3 and human BGT-1.

    References

    1. Gadea and Lopez-Colome (2001) Glial transporters for glutamate, glycine and GABA: II GABA transporters. J.Neurosci.Res. 63 461.
    2. Borden et al (1994) Tiagabine, SK&F 89976-A, Ci 966 and NNC-711 are selective for the cloned GABA transporter GAT-1. Eur.J.Pharmacol. 269 219.
    3. Bordern et al (1994) Cloning of the human homologue of the GABA transporter GAT-3 and identification of a novel inhibitor with selectivity for this site. Receptors Channels 2 207.