Modulation of heterotrimeric GTP-binding proteins in immune system and brain

We used both in vitro and in vivo models to study immuno- and neuroimmunomodulator effects on cell signalling at the cellular or organ level of brain (glioma cells) or lymphoid systems. We studied immunostimulators - interleukin 2 (IL2) or ergot alkaloid agroclavine, dopaminergic (DI) agonist, in comparison with psychotropic drugs - antidepressant fluoxetine or citalopram of selective serotonin reuptake inhibitor group (SSRI). We assayed signal transduction via heterotrimeric GTP- binding (G) proteins, and their a subunits G alphaq/11, Gas and G alpha i1,2 as well as GP subunit levels. The profiles of Ga protein subunits were analyzed using rat natural killer (NK) lymphocytes of RNK16 cell line (CD45 +/-), rat C6 glioma cell line and C6 glioma cells transfected (t) with lymphocyte phenotypic markers, prepared by us. We demonstrated similar inhibitory effects of IL2, agroclavine or fluoxetine on RNKI6 CD45(-) and C6 glioma cell G alphaq/11 subunit levels. Furthermore, adenosine receptor agonist [5'-(N-ethylcarboxamido) adenosine, NECA] effects on Get subunit profiles of C6 glioma- and RNKI6 CD45(-) cells were comparable with fluoxetine action. Different Ga profiles of(t)C6 glioma cells or RNKI6 CD45(+) lymphocytes were detected, supporting the idea about microdomain rearrangement role in G protein mediated cell signalling. Finally antidepressant citalopram induced Gee profile changes of both C6 glioma cells and brains of in vivo treated rats were comparable. Furthermore, citalopram induced changes of Ga profiles in the rat brain and the spleen were similar in contrast to distinct thymus response. We can conclude our in vitro and in vivo study, based on various experimental approaches, that the immune system and the brain can share common properties of molecular regulations during neuro-immunomodulator signal transduction.