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

We used both in vitro and in vivo models to study immuno- and neuroimmunomo dulator effects on cell signalling at the cellular or organ level of brain (glioma cells) or lymphoid systems. We studied immunostimulators - interleu kin 2 (IL2) or ergot alkaloid agroclavine, dopaminergic (DI) agonist, in co mparison with psychotropic drugs - antidepressant fluoxetine or citalopram of selective serotonin reuptake inhibitor group (SSRI). We assayed signal t ransduction via heterotrimeric GTP- binding (G) proteins, and their a subun its G alphaq/11, Gas and G alpha i1,2 as well as GP subunit levels. The pro files of Ga protein subunits were analyzed using rat natural killer (NK) ly mphocytes of RNK16 cell line (CD45 +/-), rat C6 glioma cell line and C6 gli oma cells transfected (t) with lymphocyte phenotypic markers, prepared by u s. We demonstrated similar inhibitory effects of IL2, agroclavine or fluoxe tine on RNKI6 CD45(-) and C6 glioma cell G alphaq/11 subunit levels. Furthe rmore, 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 ce lls or RNKI6 CD45(+) lymphocytes were detected, supporting the idea about m icrodomain rearrangement role in G protein mediated cell signalling. Finall y antidepressant citalopram induced Gee profile changes of both C6 glioma c ells and brains of in vivo treated rats were comparable. Furthermore, cital opram induced changes of Ga profiles in the rat brain and the spleen were s imilar in contrast to distinct thymus response. We can conclude our in vitr o and in vivo study, based on various experimental approaches, that the imm une system and the brain can share common properties of molecular regulatio ns during neuro-immunomodulator signal transduction.