Activation of mu opioid receptors sensitizes Transient Receptor Potential Vanilloid Type 1 (TRPV1) via β-arrestin-2-mediated cross-talk

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

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Article numbere93688
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 2 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Rowan, M. P., Bierbower, S. M., Eskander, M. A., Szteyn, K., Por, E. D., Gomez, R., Veldhuis, N., Bunnett, N. W., & Jeske, N. A. (2014). Activation of mu opioid receptors sensitizes Transient Receptor Potential Vanilloid Type 1 (TRPV1) via β-arrestin-2-mediated cross-talk. PloS one, 9(4), [e93688]. https://doi.org/10.1371/journal.pone.0093688