Expression and Function of Non-neuronal GABA Transporters in Human Lymphocytes

Background: Neurotransmitters not only play a key role in neuronal communication but also coordinate cell functions in non-neuronal cells, such as immune cells. Previous research reported a complete GABAergic system in human lymphocytes. In this study, focus is put on GABA transporters (GATs) and their physiological role during lymphocyte activation. Materials and Methods: Using RT-PCR and [H-3]-GABA uptake assays, GAT expression and activity was evaluated under basal conditions and in cells exposed to phytohemagglutinin (PHA) or GABA. To study GAT role, cell proliferation was evaluated by [3H]-thymidine incorporation in the presence of Nipecotic Acid (NA), a GAT inhibitor. Finally, using HPLC GABA levels were analyzed in culture supernatants. Results: In lymphocytes under any condition, at least one GAT subtype was detected. No GAT-3 was found. The PHA and GABA-treatment increased both expression and activity. In addition, GAT blockade inhibited PHA-induced lymphocyte proliferation. The GABA was detected only in PHA-treated cell supernatants, thus indicating GABA secretion at least during proliferation. Conclusion: These findings demonstrate that extraneuronal GATs affect lymphocyte functionality. Characterization of GAT roles in immune response and as a link between nervous system and immune system will provide new therapeutic targets and could help reduce side effects of current therapies.