In Vivo and In Vitro Analyses of Novel Peptidomimetic Disruptors for the Serotonin 5-HT 2C Receptor Interaction With Phosphatase and Tensin Homolog

Hypofunction of the serotonin (5-HT) 5-HT receptor (5-HT R) has been implicated in a variety of disorders including substance use disorders. As such, approaches to enhance 5-HT R signaling display therapeutic potential. In the present study, we show that disruption of the 5-HT R interaction with the...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in pharmacology 2019, Vol.10, p.907
Main Authors: Soto, Claudia A, Du, Huang-Chi, Fox, Robert G, Yang, Taegyun, Hooson, James, Anastasio, Noelle C, Gilbertson, Scott R, Cunningham, Kathryn A
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hypofunction of the serotonin (5-HT) 5-HT receptor (5-HT R) has been implicated in a variety of disorders including substance use disorders. As such, approaches to enhance 5-HT R signaling display therapeutic potential. In the present study, we show that disruption of the 5-HT R interaction with the protein phosphatase and tensin homolog (PTEN) peptidomimetics enhances 5-HT R-mediating signaling and potentiates selective 5-HT R agonists in behavioral rodent models. Overall, the present study provides further evidence that 5-HT 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.
ISSN:1663-9812
1663-9812