Participation of GABA transporters in immune response and neuro-immune communication

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

Mar del Plata

Congreso; XXX Congreso anual SAN; 2015

Sociedad Argentina de Investigación en Neurociencia

The nervous and the immune systems (NSand IS respectively) are physically and physiologically connected. Recently, expression of neurotransmitter systemcomponents in immune cells and synthesis andreceptors of cytokines in NScells were described. We previously reportedthat a complete GABAergic systemis functionally expressed in human lymphocytes. Now, we are focusing on GABA transporters (GATs).Four GATsubtypes (GAT 1-3 and BGT-1) were described in human NS. We studiedGAT mRNA levels in activated and resting lymphocytes (with and without themitogen phytohemagglutinin (PHA),respectively). GAT-2 and BGT-1 mRNAs were detected in most of activated cells. Moreover,incubation with PHA also increased [3H]GABA uptake.To evaluate the physiological role of GATs we determined cell proliferation byPHA in the presence of nipecotic acid (NA), a GAT inhibitor. Cell proliferationwas negatively modulated by NA. We also analyzed GABA levels in lymphocytecultures. We could only detect GABA in supernatant from activated cells. Despite its typical role in the synapse where they mediate cellular uptakeof GABA, under certain conditions GATs can reverse and releaseGABA. This secretion is vesicleindependent. We propose that this mechanism could be involved in GABArelease in lymphocytes. Establishing therole of endogenous GATs inimmune response and as a link between NS and IS will provide new therapeutictargets for the treatment of diseasesthat could affect both systems.