Activation of protein kinase C by the capsaicin analogue resiniferatoxin in sensory neurones

J Neurochem. 1995 Sep;65(3):1309-17. doi: 10.1046/j.1471-4159.1995.65031309.x.


Resiniferatoxin and capsaicin are sensory neurone-specific excitotoxins that operate a common cation channel in nociceptors. Resiniferatoxin is structurally similar to capsaicin and to phorbol esters. Specific [3H]-resiniferatoxin binding, which was detected in the membrane (KD value 1.8 +/- 0.2 nM) but not cytosolic fraction of rat dorsal root ganglia, could not be displaced by phorbol 12,13-dibutyrate. Conversely, resiniferatoxin did not displace [3H]phorbol 12,13-dibutyrate binding in either the cytosolic or membrane fraction. Resiniferatoxin and capsaicin both caused translocation of protein kinase C in dorsal root ganglion neurones (EC50 value 18 +/- 3 nM). This translocation was greatly reduced but not abolished, in the absence of external Ca2+, suggesting that it was secondary to Ca2+ entry. Resiniferatoxin also caused direct activation of a Ca(2+)- and lipid-dependent kinase (or kinases) in the cytosolic fraction of dorsal root ganglia, at concentrations (100 nM to 10 microM) higher than required for displacement of [3H]resiniferatoxin binding or translocation of protein kinase C. Capsaicin (up to 10 microM) was unable to mimic this effect. These data imply that although resiniferatoxin-induced translocation of protein kinase C in dorsal root ganglion neurones was mainly indirect, it also caused direct activation of a protein kinase C-like kinase in these cells.

MeSH terms

  • Animals
  • Capsaicin / pharmacology
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • Diterpenes / metabolism
  • Diterpenes / pharmacology*
  • Enzyme Activation / drug effects
  • Ganglia, Spinal / enzymology*
  • Ganglia, Spinal / metabolism
  • Ionomycin / pharmacology
  • Male
  • Neurons / enzymology*
  • Neurons / metabolism
  • Neurotoxins / pharmacology*
  • Phorbol 12,13-Dibutyrate / metabolism
  • Potassium Chloride / pharmacology
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tritium


  • Diterpenes
  • Neurotoxins
  • Tritium
  • Phorbol 12,13-Dibutyrate
  • Ionomycin
  • Potassium Chloride
  • resiniferatoxin
  • Protein Kinase C
  • Capsaicin