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

Bhave G, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW
Neuron. 2002 35 (4): 721-31

PMID: 12194871 · DOI:10.1016/s0896-6273(02)00802-4

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.

MeSH Terms (20)

Amino Acid Sequence Animals Binding Sites Capsaicin Central Nervous System CHO Cells COS Cells Cricetinae Cyclic AMP Cyclic AMP-Dependent Protein Kinases Mutation Neurons, Afferent Nociceptors Pain Phosphorylation Protein Structure, Tertiary Receptors, Drug Recombinant Fusion Proteins Serine Transfection

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