Induction of vanilloid receptor channel activity by protein kinase C

Nature. 2000 Dec;408(6815):985-90. doi: 10.1038/35050121.


Capsaicin or vanilloid receptors (VRs) participate in the sensation of thermal and inflammatory pain. The cloned (VR1) and native VRs are non-selective cation channels directly activated by harmful heat, extracellular protons and vanilloid compounds. However, considerable attention has been focused on identifying other signalling pathways in VR activation; it is known that VR1 is also expressed in non-sensory tissue and may mediate inflammatory rather than acute thermal pain. Here we show that activation of protein kinase C (PKC) induces VR1 channel activity at room temperature in the absence of any other agonist. We also observed this effect in native VRs from sensory neurons, and phorbol esters induced a vanilloid-sensitive Ca2+ rise in these cells. Moreover, the pro-inflammatory peptide, bradykinin, and the putative endogenous ligand, anandamide, respectively induced and enhanced VR activity, in a PKC-dependent manner. These results suggest that PKC may link a range of stimuli to the activation of VRs.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Arachidonic Acids / pharmacology
  • Bradykinin / pharmacology
  • Calcium / metabolism
  • Cells, Cultured
  • Endocannabinoids
  • Enzyme Activation
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Oocytes
  • Patch-Clamp Techniques
  • Phosphorylation
  • Polyunsaturated Alkamides
  • Protein Kinase C / metabolism*
  • Rats
  • Receptors, Drug / biosynthesis*
  • Receptors, Drug / drug effects
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Xenopus laevis


  • Arachidonic Acids
  • Endocannabinoids
  • Ion Channels
  • Polyunsaturated Alkamides
  • Receptors, Drug
  • Recombinant Proteins
  • adenosine 5'-O-(3-thiotriphosphate)
  • Adenosine Triphosphate
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • Bradykinin
  • Calcium
  • anandamide