In Vivo and In Vitro Analyses of Novel Peptidomimetic Disruptors for the Serotonin 5-HT2C Receptor Interaction With Phosphatase and Tensin Homolog
Hypofunction of the serotonin (5-HT) 5-HT 2C receptor (5-HT 2C R) has been implicated in a variety of disorders including substance use disorders. As such, approaches to enhance 5-HT 2C R signaling display therapeutic potential. In the present study, we show that disruption of the 5-HT 2C R interact...
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Published in | Frontiers in pharmacology Vol. 10; p. 907 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
23.08.2019
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Subjects | |
Online Access | Get full text |
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Summary: | Hypofunction of the serotonin (5-HT) 5-HT
2C
receptor (5-HT
2C
R) has been implicated in a variety of disorders including substance use disorders. As such, approaches to enhance 5-HT
2C
R signaling display therapeutic potential. In the present study, we show that disruption of the 5-HT
2C
R interaction with the protein phosphatase and tensin homolog (PTEN)
via
peptidomimetics enhances 5-HT
2C
R-mediating signaling
in vitro
and potentiates selective 5-HT
2C
R agonists in behavioral rodent models. Overall, the present study provides further evidence that 5-HT
2C
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Alfredo Meneses, Center for Research and Advanced Studies (CINVESTAV), Mexico; Nathan Pentkowski, University of New Mexico, United States; Alexey Kozlenkov, Icahn School of Medicine at Mount Sinai, United States Edited by: Stella Dracheva, Icahn School of Medicine at Mount Sinai, United States This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology |
ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2019.00907 |