title: An intrinsic GABAergic system in human lymphocytes.
abstract: γ-amino butyric acid (GABA) is an ubiquitous neurotransmitter in the central nervous system and it is also present in non-neuronal cells. In this study we investigated the presence of neuronal components of the GABAergic system in lymphocytes and its functional significance. By using RT-PCR we detected mRNA expression of different components of the GABAergic system in resting and mitogen-activated lymphocytes: i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, the vesicular protein involved in GABA storage; iii) GABA transporters (GAT-1 and GAT-2); iv) GABA-T, the enzyme that catabolizes GABA; and v) subunits that conform ionotropic GABA receptors. The presence of VIAAT protein in resting and activated cells was confirmed by immunocytochemistry. The functionality of GABA transporters was evaluated by measuring the uptake of radioactive GABA. The results show that [(3)H]GABA uptake is 5-fold higher in activated than in resting lymphocytes. To determine if GABA subunits assemble into functional channels, we performed whole-cell recordings in activated lymphocytes. GABA and muscimol, a specific agonist of ionotropic GABA receptors, elicit macroscopic currents in about 10-15% of the cells. Finally, by using [(3)H]thymidine incorporation assays, we determined that the presence of agonists of GABA receptor during activation inhibits lymphocyte proliferation. Our results reveal that lymphocytes have a functional GABAergic system, similar to the neuronal one, which may operate as a modulator of T-cell activation. Pharmacological modulation of this system may provide new approaches for regulation of T-cell response.
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca, UNS-CONICET, Camino La, Carrindanga Km 7, B8000FWB Bahía Blanca, Argentina.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Dionisio
authors.forename: María
authors.initials: M
authors.lastname: José De Rosa
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bouzat
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Esandi
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D018079:Receptors, GABA / Q000502:physiology*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000502:physiology; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; D018079:Receptors, GABA; C492245:SLC32A1 protein, human; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2