There are no clear data on the molecular mechanism by which the hippocampal 5-HT transmission contributes to the neuroprotective and antidepressant effects of 5-HT uptake blockers. Previously, we revealed that a 5-HT1A agonist may induce phosphorylation of FGFR1 and ERK1/2 in rat hippocampus independent of FGF-2, suggesting transactivation of FGFR1 tyrosine kinase in the absence of neurotrophic factor binding. As extension of previous work, using BRET analysis and coimmunoprecipitation in cellular models, FGFR1-5-HT1A heteroreceptor complexes have been demonstrated and agonist modulation characterized. In vitro assays on ERK1/2 phosphorylation in HEK cells and primary hippocampal cultures have shown synergistic increases in signaling upon coactivation with FGF-2 and 5-HT1A agonist. Coactivation of the FGFR1/5-HT1A heteroreceptor complex also resulted in synergistic increases in extensions of PC12 cells and neurite densities and protrusions in primary hippocampal cultures. The findings indicate that neurotrophic effects of 5-HT in brain may in part be mediated by activation of the 5-HT1A receptor in the hippocampal FGFR1/5-HT1A heteroreceptor complex enhancing the FGFR1 signaling and playing a significant role in hippocampal plasticity.

Frinchi, M., Borroto-Escuela, D.O., Romero-Fernandez, W., Di Liberto, V., Mudò, G., Agnati, L.F., et al. (2011). Neuronal FGFR1 transactivation by inducing FGFR1/5-HT1A heteroreceptor complexes formation. ACTA PHYSIOLOGICA, 203(suppl 686).

Neuronal FGFR1 transactivation by inducing FGFR1/5-HT1A heteroreceptor complexes formation

FRINCHI, Monica;DI LIBERTO, Valentina;MUDO', Giuseppa;BELLUARDO, Natale;
2011-01-01

Abstract

There are no clear data on the molecular mechanism by which the hippocampal 5-HT transmission contributes to the neuroprotective and antidepressant effects of 5-HT uptake blockers. Previously, we revealed that a 5-HT1A agonist may induce phosphorylation of FGFR1 and ERK1/2 in rat hippocampus independent of FGF-2, suggesting transactivation of FGFR1 tyrosine kinase in the absence of neurotrophic factor binding. As extension of previous work, using BRET analysis and coimmunoprecipitation in cellular models, FGFR1-5-HT1A heteroreceptor complexes have been demonstrated and agonist modulation characterized. In vitro assays on ERK1/2 phosphorylation in HEK cells and primary hippocampal cultures have shown synergistic increases in signaling upon coactivation with FGF-2 and 5-HT1A agonist. Coactivation of the FGFR1/5-HT1A heteroreceptor complex also resulted in synergistic increases in extensions of PC12 cells and neurite densities and protrusions in primary hippocampal cultures. The findings indicate that neurotrophic effects of 5-HT in brain may in part be mediated by activation of the 5-HT1A receptor in the hippocampal FGFR1/5-HT1A heteroreceptor complex enhancing the FGFR1 signaling and playing a significant role in hippocampal plasticity.
2011
62° Congresso annuale della Società Italiana di Fisiologia
Sorrento
25-27 Settembre 2011
62
Frinchi, M., Borroto-Escuela, D.O., Romero-Fernandez, W., Di Liberto, V., Mudò, G., Agnati, L.F., et al. (2011). Neuronal FGFR1 transactivation by inducing FGFR1/5-HT1A heteroreceptor complexes formation. ACTA PHYSIOLOGICA, 203(suppl 686).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/63412
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