Over the past decade, many examples of activation of receptor tyrosine kinasesin response to G-protein coupled receptor signaling have been reported,indicating that there are alternative modes of receptor tyrosine kinaseactivation (transactivation) in the absence of neurotrophic factor binding. Inthe present work, we aimed to examine if 5-HT receptor subtype activationmay induce fibroblast growth factor receptor-1 (FGFR1) phosphorylationthrough transactivation of tyrosine kinase. The study has been performedin young adult rats treated with the selective 5-HT1A receptor agonist 8-OHDPATat the dose of 0.4 mg/kg/i.p.. FGFR1 phosphorylation was evaluated byimmunoprecipitation and western blotting in a time-course study rangingbetween 15 min and 24h. Among the brain regions, target of the 5-HTinnervations, examined in this study (cingulate and frontal cortices, andthe hippocampus), only in the hippocampus the FGFR1 phosphorylationwas found upregulated 24 h following 8-OH-DPAT treatment. This FGFR1activation was independent of its ligand FGF-2 changes, and using primarycultures of hippocampal neurons the FGFR1 transactivation by 5-HTreceptors was further defined. The existence of FGFR1 transactivation inresponse to 5-HT receptor activation will increase our understanding themechanisms of antidepressant drug effects, since 5-HT receptors have beenimplicated in anxiety and depression.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2010|