The neuronal GABAergic system in human lymphocytes

DIONISIO LEONARDO; DE ROSA MARIA JOSE; BOUZAT CECILIA; ESANDI MARÍA DEL CARMEN

Huerta Grande, Córdoba, Argentina.

Congreso; I Reunión Conjunta Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias.; 2009

SAN/ Taller Argentino de Neurociencia

γ-Amino butyric acid (GABA) is an ubiquitous neurotransmitter in the central nervous system but it is also present in non neuronal cells. The goal of this study was to determine the neuronal components of the GABAergic system in lymphocytes and their functional significance. Using RT-PCR we determined mRNA expression of different components of this system in resting and mitogen activated lymphocytes (PHA 10 µg/mL): i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, the vesicular protein involved in GABA storage; iii) GABA transporters (GAT1 and GAT2); iv) GABA-T, the enzyme that catabolizes GABA; v) alpha subunits (alpha1-6) of GABAA receptor; and vi) rho 2 subunit of the GABAC receptor. The functionality of the transporters was evaluated by measuring the uptake of radioactive GABA. The results demonstrated that the 3[H]GABA uptake is 5-fold higher in activated lymphocytes than in resting ones. Using 3[H]thymidine incorporation, we established that GABA and muscimol are able to modulate lymphocyte proliferation. Finally, we demonstrated that these GABA receptor agonists are capable to elicit macroscopic currents in activated lymphocytes. Our results revealed that lymphocytes have most of the essential components needed to constitute a GABAergic system. Pharmacological modulation of this system may provide new approaches for regulation of T cell response.