Characterization of a neuronal ? like GABAergic system in human lymphocytes

DE ROSA MJ; DIONISIO L; BOUZAT, C; ESANDI MDEL C

San Diego, CA

Congreso; 40 TH Annual Meeting of the Society for Neuroscience; 2010

Society for Neuroscience

The functionality of the transporters was evaluated by measuring uptake of radioactive GABA. The results demonstrated that the uptake of GABA is significantly higher in activated lymphocytes than in resting ones. In addition we performed immunocytochemistry to detect VIAAT protein and real time PCR to quantify the mRNA levels of GABA-T. We observed upregulation of VIAAT and GABA-T upon mitogen stimulation. To determine if GABA subunits assemble into functional channels, we performed whole-cell recordings in activated lymphocytes. GABA and Muscimol, a specific agonist for ionotropic GABA receptors, elicits macroscopic currents in about 20-30% of the cells that exhibits different kinetic properties. These experiments show that lymphocytes express functional GABAA channels, and suggest that different types of GABAA receptors are present. Finally, using [3H]thymidine incorporation, we established that GABA is able to modulate negatively lymphocyte proliferation. Muscimol, similarly to GABA, inhibits lymphocyte proliferation. These data demonstrate that ionotropic GABA receptors are the main modulators of the immune-suppressive effects of GABA. Our results revealed that lymphocytes have most of the essential components needed to constitute a non-neuronal GABAergic system. Pharmacological modulation of this system may provide new approaches for regulation of T cell response. Furthermore, elucidation of its function will contribute to clarify the interactions between the nervous and immune systems.