GABA transporters in human lymphocytes

DE ROSA, M.J.; DIONISIO, L.; CALDIRONI H. ; BOUZAT, C.

Huerta Grande, Córdoba

Congreso; XXVIII Reunión Anual de SAN; 2013

SAN

GABA is the main inhibitory neurotransmitter in CNS and is associated to severalneurological disorders. GABA transporters (GATs) play a critical role in GABA levelregulation 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 acomplete GABAergic system in lymphocytes. Here, we studied the modulation ofthe expression and activity of GATs in human lymphocytes by the mitogenphytohemagglutinin (PHA). We determined mRNA GAT expression in activated andresting cells (with and without PHA, respectively). GAT 3 was not detected underany 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 theseobservations, incubation with PHA also increased [3H]GABA uptake. To evaluatethe physiological role of GATs we determined cell proliferation by PHA in thepresence of nipecotic acid (NA), a GAT inhibitor. Cell proliferation was negativelymodulated by NA. In addition, secreted GABA was detected only in supernatantfrom activated lymphocyte cultures. Taken together, our results show thatlymphocytes express functional GATs whose expression is modulated by PHA, GATsregulate cell proliferation, and lymphocyte cells have the ability to secrete GABA.Pharmacological modulation of GATs present in lymphocytes could be a new targetto modulate immune response.