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

ABSTRACT: Hypofunction of the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) has been implicated in a variety of disorders including substance use disorders. As such, approaches to enhance 5-HT2CR signaling display therapeutic potential. In the present study, we show that disruption of the 5-HT2CR interaction with the protein phosphatase and tensin homolog (PTEN) via peptidomimetics enhances 5-HT2CR-mediating signaling in vitro and potentiates selective 5-HT2CR agonists in behavioral rodent models. Overall, the present study provides further evidence that 5-HT2CR 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.

SUBMITTER: Soto CA 

PROVIDER: S-EPMC6716272 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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<i>In Vivo</i> and <i>In Vitro</i> Analyses of Novel Peptidomimetic Disruptors for the Serotonin 5-HT<sub>2C</sub> Receptor Interaction With Phosphatase and Tensin Homolog.

Soto Claudia A CA   Du Huang-Chi HC   Fox Robert G RG   Yang Taegyun T   Hooson James J   Anastasio Noelle C NC   Gilbertson Scott R SR   Cunningham Kathryn A KA  

Frontiers in pharmacology 20190823

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) <i>via</i> peptidomimetics enhances 5-HT<sub>2C</sub>R-mediating signaling <i>in vitro</i> and potentiat  ...[more]

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