title: Activation of 5-HT7 receptors increases neuronal platelet-derived growth factor β receptor expression.
abstract: 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 Gα(s) 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.
authors.affiliation: Department of Biology, University of Waterloo, ON, Canada.
authors.forename: Maryam S
authors.initials: MS
authors.lastname: Vasefi
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Kruk
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: John J
authors.initials: JJ
authors.lastname: Heikkila
authors.forename: Michael A
authors.initials: MA
authors.lastname: Beazely
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D020797:Receptor, Platelet-Derived Growth Factor beta; D017868:Cyclic AMP-Dependent Protein Kinases