The reuptake of Neurotransmitters (NTs) by specific transporters in the CNS insures termination of synaptic signalling, the maintenance of low basal extracellular levels of NTs and their recycling. There are evidences that some NT transporters can also release the NT from the presynaptic membrane, but results are still controversial.

The reverse mode of operation of the GABA transporter GAT1 was investigated in Xenopus laevis oocytes transfected with the transporter's cRNA .

In oocytes injected with GABA dissolved in NaCl solution (final GABA concentration about 10 mM), the transport current elicited by 300 mM external GABA showed an apparent inward behavior not present in non-injected oocytes.

In the same injected oocytes and in absence of external GABA, an outward current was visible that was blocked by the addition of the GAT1 inhibitor SKF89976-A .

Subtracting the I/V curves in presence of blocker from those in its absence gives the outward current due to the reverse transport of GAT1.

The outward current obtained in this way was not observed in oocytes injected only with the NaCl solution without GABA.

The intracellular injection of GABA together with SKF89976-A is still under investigation, but preliminary results seem to show that SKF89976-A is able to block GAT1 even from the inner side of membrane.

These initial results, indicate that GAT1 is able to operate the reverse transport and enhance the understanding of the conditions for its establishment.