Insulin and insulin-like growth factor type-I up-regulate the vanilloid receptor-1 (TRPV1) in stably TRPV1-expressing SH-SY5Y neuroblastoma cells

J Neurosci Res. 2007 May 15;85(7):1413-9. doi: 10.1002/jnr.21255.


The capsaicin receptor, transient receptor potential, vanilloid type 1 (TRPV1), is a Ca(2+)-permeable ion channel activated by noxious stimuli eliciting pain. Several reports have shown modulation of TRPV1 activity and expression by neuronal growth factors. Here, we study the long-term effects on TRPV1 expression mediated by insulin-like growth factor type-I (IGF-I) and insulin in a stably TRPV1-expressing SH-SY5Y neuroblastoma cell line. We show that, after 72 hr of 10 nM IGF-I or insulin exposure, the TRPV1 protein level was up-regulated 2.5- and 2-fold, respectively. By blocking phosphatidylinositol-3-kinase [PI(3)K] or mitogen-activated protein kinase (MAPK) signaling, we concluded that the increase in total TRPV1 protein content induced by IGF-I was controlled by PI(3)K signaling, whereas insulin seemed to regulate TRPV1 protein expression via both PI(3)K and MAPK pathways. Inhibiting protein kinase C (PKC) blocked the effects of both IGF-I and insulin. Furthermore, the concentrations causing a 50% Ca(2+) increase (EC(50)) after insulin and IGF-I treatments were significantly lowered compared with untreated cells. We conclude that IGF-I and insulin enhance TRPV1 protein expression and activity, and impaired pain sensation might result from distorted TRPV1 regulation in the peripheral nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Calcium / metabolism
  • Cell Line, Tumor
  • Humans
  • Insulin / physiology*
  • Insulin-Like Growth Factor I / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Neuroblastoma / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase C / metabolism
  • Signal Transduction / physiology*
  • TRPV Cation Channels / metabolism*
  • Transfection
  • Up-Regulation


  • Insulin
  • TRPV Cation Channels
  • TRPV1 receptor
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • Calcium