2012; 33(6): 614-618
PubMed PMID: 23160219
Adenosine-5'-(N-ethylcarboxamide):pharmacology, Animals, Brain Neoplasms, Cell Line, Tumor, Citalopram:pharmacology, Depression:drug therapy, Fluoxetine:pharmacology, GTP-Binding Protein alpha Subunits, Gq-G11:metabolism, Glioma, Neurons:cytology, Puriner.
OBJECTIVES: Trimeric G-proteins play a crucial role in the transmembrane signalling to intracellular pathways via effector phospholipase C (1,4,5 IP3) or adenylylcyclase (cAMP). G-protein modulation is considered to participate in the antidepressant mode of action by neurotransmitter G-protein coupled receptors (GPCR). Adenosine is naturally occured nucleoside and adenosine receptor belongs to GPCR family. Properties and functions of ubiquitous adenosine receptor were described with number of agonists and antagonists.
METHODS: In C6 glioma cells, we studied acute administration of SSRI antidepressants - fluoxetine, sertraline and citalopram. We used immunochemical estimation (ELISA) of the main types of G-protein alpha subunits from isolated membranes of C6 glioma cells. We also estimated effect of NECA agonist on fluoxetine induced signalling via 1,4,5 IP3 and its levels.
RESULTS: Results show involvement of the antidepressant drugs in the C6 glioma signal transduction cascades and their modulation in dependence on the antidepressant of SSRI type. We measured main G alpha protein profiles after fluoxetine, sertraline and citalopram administration. We found significant changes as following: decreased G alpha Gq/11 for fluoxetine, low G alpha s for sertraline and both high G alpha q/11 and high G alpha s for citalopram. Furthermore the NECA (5´-N-ethylcarboxamido- adenosine) agonist of adenosine receptor alone evoked high decrease of G alpha q/11 levels. Whereas fluoxetine influenced G alpha q/11 decline was abolished by NECA in concentration manner, especially at 10-8 and 10-9 M concentrations. These results support abolishion NECA effect on fluoxetin influenced 1,4,5 IP3 signalling via PLC.
CONCLUSION: Main G alpha profiles are dependent on SSRI type antidepressant. Abolishing both fluoxetine evoked G alpha q/11 and and 1,4,5 IP3 signalling can indicate parallel interference between G-protein coupled receptors (GPCR) and the cell response. Presented data are first findings about adenosine receptor interaction with fluoxetine signalling. Thus in vitro studies contribute to the clarification of the molecular basis of antidepressant action....