AUTHOR=Soto Claudia A. , Du Huang-Chi , Fox Robert G. , Yang Taegyun , Hooson James , Anastasio Noelle C. , Gilbertson Scott R. , Cunningham Kathryn A. 

TITLE=In Vivo and In Vitro Analyses of Novel Peptidomimetic Disruptors for the Serotonin 5-HT2C Receptor Interaction With Phosphatase and Tensin Homolog

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00907

DOI=10.3389/fphar.2019.00907

ISSN=1663-9812

ABSTRACT=<p>Hypofunction of the serotonin (5-HT) 5-HT<sub>2C</sub> receptor (5-HT<sub>2C</sub>R) has been implicated in a variety of disorders including substance use disorders. As such, approaches to enhance 5-HT<sub>2C</sub>R signaling display therapeutic potential. In the present study, we show that disruption of the 5-HT<sub>2C</sub>R interaction with the protein phosphatase and tensin homolog (PTEN) <italic>via</italic> peptidomimetics enhances 5-HT<sub>2C</sub>R-mediating signaling <italic>in vitro</italic> and potentiates selective 5-HT<sub>2C</sub>R agonists in behavioral rodent models. Overall, the present study provides further evidence that 5-HT<sub>2C</sub>R activity can be modulated through an allosteric protein–protein interaction. This work provides the groundwork for the continued exploration of protein–protein interactions that can allosterically modulate this critical receptor and other important G protein-coupled receptors (GPCRs) for new therapeutic development through mechanisms that may display clinical utility.</p>