A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1

Nathaniel A. Jeske, Anibal Diogenes, Nikita B. Ruparel, Jill C. Fehrenbacher, Michael Henry, Armen N. Akopian, Kenneth M. Hargreaves

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-kinase anchoring protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, we investigated the functional involvement of AKAP150 in mediating sensitization of TRPV1, and found that AKAP150 is co-expressed in trigeminal ganglia (TG) neurons from rat and associates with TRPV1. Furthermore, siRNA-mediated knock-down of AKAP150 expression led to a significant reduction in PKA phosphorylation of TRPV1 in cultured TG neurons. In CHO cells, the PKA RII binding site on AKAP was necessary for PKA enhancement of TRPV1-mediated Ca2+-accumulation. In addition, AKAP150 knock-down in cultured TG neurons attenuated PKA sensitization of TRPV1 activity and in vivo administration of an AKAP antagonist significantly reduced prostaglandin E2 sensitization to thermal stimuli. These data suggest that AKAP150 functionally regulates PKA-mediated phosphorylation/sensitization of the TRPV1 receptor.

Original languageEnglish (US)
Pages (from-to)604-616
Number of pages13
JournalPain
Volume138
Issue number3
DOIs
StatePublished - Sep 15 2008
Externally publishedYes

Keywords

  • AKAP
  • Hyperalgesia
  • PKA
  • Pain
  • TRPV1
  • Trigeminal

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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    Jeske, N. A., Diogenes, A., Ruparel, N. B., Fehrenbacher, J. C., Henry, M., Akopian, A. N., & Hargreaves, K. M. (2008). A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1. Pain, 138(3), 604-616. https://doi.org/10.1016/j.pain.2008.02.022