cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation

Gautam Bhave, Weiguo Zhu, Haibin Wang, D. J. Brasier, Gerry S. Oxford, Robert W. Gereau IV

Research output: Contribution to journalArticle

422 Scopus citations

Abstract

The capsaicin receptor, VR1 (also known as TRPV1), is a ligand-gated ion channel expressed on nociceptive sensory neurons that responds to noxious thermal and chemical stimuli. Capsaicin responses in sensory neurons exhibit robust potentiation by cAMP-dependent protein kinase (PKA). In this study, we demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1. In vitro phosphorylation, phosphopeptide mapping, and protein sequencing of VR1 cytoplasmic domains delineate several candidate PKA phosphorylation sites. Electrophysiological analysis of phosphorylation site mutants clearly pinpoints Ser116 as the residue responsible for PKA-dependent modulation of VR1. Given the significant roles of VR1 and PKA in inflammatory pain hypersensitivity, VR1 phosphorylation at Ser116 by PKA may represent an important molecular mechanism involved in the regulation of VR1 function after tissue injury.

Original languageEnglish (US)
Pages (from-to)721-731
Number of pages11
JournalNeuron
Volume35
Issue number4
DOIs
StatePublished - Aug 15 2002

ASJC Scopus subject areas

  • Neuroscience(all)

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