Modulation of TRPV1 by nonreceptor tyrosine kinase, c-Src kinase

Am J Physiol Cell Physiol. 2004 Aug;287(2):C558-63. doi: 10.1152/ajpcell.00113.2004. Epub 2004 Apr 14.


The capsaicin receptor TRPV1 is a nonselective cation channel that is expressed in sensory neurons. In this study, we examined the role of the nonreceptor cellular tyrosine kinase c-Src kinase in the modulation of the rat TRPV1. Capsaicin-induced currents in identified colonic dorsal root ganglion neurons were blocked by the c-Src kinase inhibitor PP2 and enhanced by the tyrosine phosphatase inhibitor sodium orthovandate. PP2 also abolished currents in human embryonic kidney-293 cells transfected with rat TRPV1, whereas cotransfection of TRPV1 with v-Src resulted in fivefold increase in capsaicin-induced currents. In cells transfected with dominant-negative c-Src and TRPV1, capsaicin-induced currents were decreased by approximately fourfold. TRPV1 co-immunoprecipitated with Src kinase and was tyrosine phosphorylated. These studies demonstrate that TRPV1 is a potential target for cellular tyrosine kinase-dependent phosphorylation.

Publication types

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

MeSH terms

  • Animals
  • CSK Tyrosine-Protein Kinase
  • Capsaicin / pharmacology
  • Cell Line
  • Ganglia, Spinal / cytology
  • Humans
  • Kidney / cytology
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons, Afferent / cytology
  • Neurons, Afferent / enzymology*
  • Nociceptors / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / metabolism*
  • src-Family Kinases


  • Receptors, Drug
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • Capsaicin