Abstract
cDNA clones encoding two novel gamma-aminobutyric acid (GABA) transporters (designated GAT-2 and GAT-3) have been isolated from rat brain, and their functional properties have been examined in mammalian cells. The transporters display high affinity for GABA (Km approximately 10 microM) and exhibit pharmacological properties distinct from the previously cloned neuronal GABA transporter (GAT-1). Both transporters require sodium and chloride for transport activity. The nucleotide sequences of GAT-2 and GAT-3 predict proteins of 602 and 627 amino acids, respectively, which can be modeled with 12 transmembrane domains, similar to the topology proposed for other cloned neurotransmitter transporters. Localization studies indicate that both transporters are present in brain and retina, while GAT-2 is also present in peripheral tissues. The cloning of these transporter genes from rat brain reveals previously undescribed heterogeneity in GABA transporters.
Highlights
CDNA clones encoding two novel y-aminobutyric acid (GABA) transporters have been isolated from rat brain, and their functional properties have been examined in mammalian cells
The nucleotide sequences of GABA transporters (GAT-)2 and GAT-3 predict proteins of 602 and 627 amino acids, respectively, which can be modeled with 12 transmembrane domains, similar to the topology proposed for other cloned neurotransmitter transporters
Transmission is terminated by the rapid uptake of neurotransmitter via specific, high affinity transporters located in the presynaptic terminal and/orsurrounding glial cells (1).Since inhibition of uptake by pharmacologic agents increases the levels of neurotransmitter in the synapse, and thusenhances synaptic transmission, neurotransmitter transporters provide important targets for therapeutic intervention
Summary
CDNA clones encoding two novel y-aminobutyric acid (GABA) transporters (designated GAT-2 and GAT-3) have been isolated from rat brain, and their functional properties have been examined in mammalian cells. Localization studies indicate that both transportersare present in brain andretina, while GAT-2is present in peripheraltissues Thecloning of these transporter genes from rat brain reveals previously undescribedheterogeneity in GABA transporters. A GABA transporter with neuronal-type pharmacology designated GAT-1 has previously been purified and cloned (12), but the molecular properties of other GABA transporters including glial transporter(s) have not yet been elucidated. Cloning and Sequencing-A rat brain cDNA library in the Lambda ZAP I1 vector (Stratagene, La Jolla, CA) was screened at low stringency using probes representing the complete coding region of the rat GABA transporter cDNA (GAT-1, Ref. 12). After 10 min the medium was removed, and a solution containing [3H]GABA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
