GABA transporters in human lymphocytes

Abstract

GABA is the main inhibitory neurotransmitter in CNS and is associated to several neurological disorders. GABA transporters (GATs) play a critical role in GABA level regulation by allowing re-uptake of neuronal secreted GABA. Four GAT subtypes (GAT 1-3 and BGT-1) have been described in humans. Previously, we reported a complete GABAergic system in lymphocytes. Here, we studied the modulation of the expression and activity of GATs in human lymphocytes by the mitogen phytohemagglutinin (PHA). We determined mRNA GAT expression in activated and resting cells (with and without PHA, respectively). GAT 3 was not detected under any condition, whereas GAT 2 and BGT-1 were detected in all activated cells. Expression of GAT 1 was variable among samples and conditions. In line with these observations, incubation with PHA also increased [3H]GABA uptake. To evaluate the physiological role of GATs we determined cell proliferation by PHA in the presence of nipecotic acid (NA), a GAT inhibitor. Cell proliferation was negatively modulated by NA. In addition, secreted GABA was detected only in supernatant from activated lymphocyte cultures. Taken together, our results show that lymphocytes express functional GATs whose expression is modulated by PHA, GATs regulate cell proliferation, and lymphocyte cells have the ability to secrete GABA. Pharmacological modulation of GATs present in lymphocytes could be a new target to modulate immune response.