Activation of 5-HT7 receptors increases neuronal platelet-derived growth factor β receptor expression

• Published in: Neuroscience letters Vol. 511; no. 2; pp. 65 - 69
• Main Authors: Vasefi, Maryam S., Kruk, Jeff S., Liu, Hui, Heikkila, John J., Beazely, Michael A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 09.03.2012
• Subjects: 5-HT7; Animals; Cell Line; Cells, Cultured; Cortex; Cyclic AMP-Dependent Protein Kinases - metabolism; Drugs; Gene Expression; Hippocampus; Mice; Nervous system; Neuroleptics; Neurons; Neurons - enzymology; Neurons - metabolism; PDGF; Phospholipase C; Phosphorylation; Platelet-derived growth factor; platelet-derived growth factor B; Protein expression; Protein kinase; Psychosis; Receptor mechanisms; Receptor, Platelet-Derived Growth Factor beta - genetics; Receptor, Platelet-Derived Growth Factor beta - metabolism; Receptors, Serotonin - metabolism; Schizophrenia; Serotonin; Serotonin receptors; Signal transduction; Tyrosine; Up-Regulation; 5-CT; 5-HT7; PDGF; PLC; NMDA; Schizophrenia; Protein expression; Hippocampus
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2012.01.016

► Treatment of neurons with 5-HT7 receptor agonist results in an up-regulation of PDGF receptor protein expression. ► PDGF receptors have an increased basal phosphorylation state after 5-HT7 receptor activation. ► 5-HT7 receptor increases PDGF receptor expression in primary hippocampal, cortical neurons and SH-SY5Y cells. Several antipsychotics have a high affinity for 5-HT7 receptors yet despite intense interest in the 5-HT7 receptor as a potential drug target to treat psychosis, the function and signaling properties of 5-HT7 receptors in neurons remain largely uncharacterized. In primary mouse hippocampal and cortical neurons, as well as in the SH-SY5Y cell line, incubation with 5-HT, 5-carboxamidotryptamine (5-CT), or 5-HT7 receptor-selective agonists increases the expression of platelet-derived growth factor (PDGF)β receptors. The increased PDGFβ receptor expression is cyclic AMP-dependent protein kinase (PKA)-dependent, suggesting that 5-HT7 receptors couple to Gαs in primary neurons. Interestingly, up-regulated PDGFβ receptors display an increased basal phosphorylation state at the phospholipase Cγ-activating tyrosine 1021. This novel linkage between the 5-HT7 receptor and the PDGF system may be an important GPCR-neurotrophic factor signaling pathway in neurons.