Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Activation of mu opioid receptors sensitizes transient receptor potential vanilloid type 1 (TRPV1) via β-arrestin-2-mediated cross-talk.

Authors: Matthew P Rowan, Sonya M Bierbower, Michael A Eskander, Kalina Szteyn, Elaine D Por, Ruben Gomez, Nicholas Veldhuis, Nigel W Bunnett, Nathaniel A Jeske

Journal, date & volume: PLoS ONE, 2014 , 9, e93688

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24695785

Abstract
The transient receptor potential family V1 channel (TRPV1) is activated by multiple stimuli, including capsaicin, acid, endovanilloids, and heat (>42C). Post-translational modifications to TRPV1 result in dynamic changes to the sensitivity of receptor activation. We have previously demonstrated that β-arrestin2 actively participates in a scaffolding mechanism to inhibit TRPV1 phosphorylation, thereby reducing TRPV1 sensitivity. In this study, we evaluated the effect of β-arrestin2 sequestration by G-protein coupled receptors (GPCRs) on thermal and chemical activation of TRPV1. Here we report that activation of mu opioid receptor by either morphine or DAMGO results in β-arrestin2 recruitment to mu opioid receptor in sensory neurons, while activation by herkinorin does not. Furthermore, treatment of sensory neurons with morphine or DAMGO stimulates β-arrestin2 dissociation from TRPV1 and increased sensitivity of the receptor. Conversely, herkinorin treatment has no effect on TRPV1 sensitivity. Additional behavioral studies indicate that GPCR-driven β-arrestin2 sequestration plays an important peripheral role in the development of thermal sensitivity. Taken together, the reported data identify a novel cross-talk mechanism between GPCRs and TRPV1 that may contribute to multiple clinical conditions.