5-HT1A receptors transactivate the platelet-derived growth factor receptor type beta in neuronal cells

Fluoxetine-induced transactivation of the platelet-derived growth factor type β receptor reveals a novel heterologous desensitization process

“…1B). Moreover, we have previously demonstrated that the 5-HT receptor agonist (for subtypes 1, 5 and 7), 5-carboxamidotryptamine (5-CT), can transactivate PDGFβ receptors in SH-SY5Y cells (Kruk et al, 2013b). Fluoxetine pretreatment similarly attenuated 5-CT-induced PDGFβ receptor transactivation (Fig.…”

“…In addition to ligand-induced activation of PDGF receptors, several GPCR agonists including angiotensin II (Heeneman et al, 2000;Wang et al, 2008), dopamine (Oak et al, 2001), endothelin (Gomez Sandoval and Anand-Srivastava, 2011), sphingosine-1-phosphate (Tanimoto et al, 2004), lysophosphatidic acid (Goppelt-Struebe et al, 2000;Wang et al, 2003), and leukotrienes (McMahon et al, 2002) can induce a PDGF-independent PDGF receptor activation, a process known as transactivation. We have recently shown that 5-HT can transactivate PDGFβ receptors in neurons and have elucidated many of the components of this pathway: 5-HT binds Gα i -coupled (and possibly Gα q -coupled) 5-HT receptors, leading to PLC-and calciumdependent PKC activity, and NADPH oxidase that mediates the production of low concentrations of reactive oxygen species (Kruk et al, 2013a(Kruk et al, , 2013b. 5-HT-induced transactivation of the PDGFβ receptor is not dependent on PDGF ligand release, confirming it is a strictly intracellular pathway (Kruk et al, 2013b).…”

“…We have recently shown that 5-HT can transactivate PDGFβ receptors in neurons and have elucidated many of the components of this pathway: 5-HT binds Gα i -coupled (and possibly Gα q -coupled) 5-HT receptors, leading to PLC-and calciumdependent PKC activity, and NADPH oxidase that mediates the production of low concentrations of reactive oxygen species (Kruk et al, 2013a(Kruk et al, , 2013b. 5-HT-induced transactivation of the PDGFβ receptor is not dependent on PDGF ligand release, confirming it is a strictly intracellular pathway (Kruk et al, 2013b). In 2007, Liu et al reported that the SSRI fluoxetine was able to block 5-HT-induced PDGFβ receptor transactivation in smooth muscle cells (Liu et al, 2007).…”

“…We and others have previously shown that dopamine receptors also transactivate PDGFβ receptors (Kruk et al, 2013b;Oak et al, 2001). Given that fluoxetine and 5-HT are acting at 5-HT receptors, we sought to determine if the desensitization of transactivation could be observed with two distinct GPCR systems.…”

Ligand-Independent Activation of Platelet-Derived Growth Factor Receptor β during Human Immunodeficiency Virus–Transactivator of Transcription and Cocaine-Mediated Smooth Muscle Hyperplasia

“…Many stimuli, such as heat shock, hypoxia (40), or G protein-coupled receptor activation (41), and agents, such as deoxycholic acid, are known to cause ligand-independent activation of growth factor receptors (42). Lysophosphatidic acid has previously been reported to cause ligand-independent activation of PDGFRb (43).…”