International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2017.205.211DionisioL. CaldironiH. RosaM.J. De 22017132Background: 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 [3H]-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.]]>Schousboe, A., K.K. Madsen, M.L. Barker-Haliski and H.S. White,20143919801987Schmidt, D., L. Gram, M. Brodie, G. Kramer, E. Perucca, R. Kalviainen and C.E. Elger,200041245251Meldrum, B.S. and M.A. Rogawski,200741861Braun, M., R. Ramracheya, M. Bengtsson, A. Clark, J.N. Walker, P.R. Johnson and P. Rorsman,20105916941701Bhat, R., R. Axtell, A. Mitra, M. Miranda, C. Lock, R.W. Tsien and L. Steinman,201010725802585Pramod, A.B., J. Foster, L. Carvelli and L.K. Henry,201334197219Wu, Y., W. Wang, A. Diez-Sampedro and G.B. Richerson,200756851865Kersante, F., S.C. Rowley, I. Pavlov, M. Gutierrez-Mecinas and A. Semyanov et al.,201359124292441Christiansen, B., A.K. Meinild, A.A. Jensen and H. Brauner-Osborne,20072821933119341Dionisio, L., M.J. De Rosa, C. Bouzat and M.D.C. Esandi,201160513519Rasola, A., L.J.V. Galietta, V. Barone, G. Romeo and S. Bagnasco,1995373229233Levite, M.,20088460471Freire-Garabal, M., M.J. Nunez, J. Balboa, L.A. Garcia-Vallejo, S. Argibay, E. Rodrigo and M. Rey-Mendez,20033423336Eikelenboom, P., W.J.G. Hoogendijk, C. Jonker and W. van Tilburg,200236269280Stadelmann, C.,201124224229Wang, Y., D. Feng, G. Liu, Q. Luo and Y. Xu et al.,200818182268236Wang, Y., Q. Luo, Y. Xu, D. Feng, J. Fei, Q. Cheng and L. Xu,200918334883495Paul, A.M., W.G. Branton, J.G. Walsh, M.J. Polyak, J.Q. Lu, G.B. Baker and C. Power,20142732438De Rosa, M.D.J., M.C. Esandi, A. Garelli, D. Rayes and C. Bouzat,2005160154161Su, J., J. Yin, W. Qin, S. Sha, J. Xu and C. Jiang,201540621627Deken, S.L., M.L. Beckman, L. Boos and M.W. Quick,200039981003Lee, S., B.E. Yoon, K. Berglund, S.J. Oh and H. Park et al.,2010330790796Diaz, M.R., A. Wadleigh, B.A. Hughes, J.J. Woodward and C.F. Valenzuela,20112011Wu, Y., W. Wang and G.B. Richerson,20038920212034Takahashi, K., S. Miyoshi, A. Kaneko and D.R. Copenhagen,199545457473Basta-Kaim, A., B. Budziszewska, M. Leskiewicz, M. Kubera and G. Jagla et al.,200860925932Pistovcakova, J., M. Dostalek, A. Sulcova and D. Jezova,2008415459Vasileiou, I., T. Xanthos, E. Koudouna, D. Perrea, C. Klonaris, A. Katsargyris and L. Papadimitriou,200960518Bjurstom, H., J.Y. Wang, I. Ericsson, M. Bengtsson and Y. Liu et al.,20082054450Prud'homme, G.J., Y. Glinka and Q. Wang,20151410481056Reyes-Garcia, M.G., F. Hernandez-Hernandez, B. Hernandez-Tellez and F. Garcia-Tamayo,2007A receptor subunits RNA expression in mice peritoneal macrophages modulate their IL-6/IL-12 production.]]>1886468Nigam, R., H. El-Nour, B. Amatya and K. Nordlind,2010A receptor expression on immune cells in psoriasis: A pathophysiological role.]]>302507515