PLoS One. 2014 Apr 2;9(4):e93688. doi: 10.1371/journal.pone.0093688. eCollection 2014.

Activation of mu opioid receptors sensitizes transient receptor potential vanilloid type 1 (TRPV1) via beta-arrestin-2-mediated cross-talk.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Rowan, M. P., Bierbower, S. M., Eskander, M. A., Szteyn, K., Por, E. D., Gomez, R., Veldhuis, N., Bunnett, N. W., Jeske, N. A.,
["Department of Oral and Maxillofacial Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.", "Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.", "Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.", "Department of Oral and Maxillofacial Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.", "Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.", "Department of Oral and Maxillofacial Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.", "Departments of Pharmacology and Medicine, Monash Institute of Pharmacological Sciences, Parkville, Victoria, Australia.", "Departments of Pharmacology and Medicine, Monash Institute of Pharmacological Sciences, Parkville, Victoria, Australia.", "Department of Oral and Maxillofacial Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America."]
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 beta-arrestin2 actively participates in a scaffolding mechanism to inhibit TRPV1 phosphorylation, thereby reducing TRPV1 sensitivity. In this study, we evaluated the effect of beta-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 beta-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 beta-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 beta-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.
PMID: 24695785External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Ƣ-arrestin 2 Co-immunoprecipitation Rat trigeminal (TG) ganglia 24695785
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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