Abstract
Nociceptors, or pain-sensitive receptors, are unique among sensory receptors in that their sensitivity is increased by noxious stimulation. This process, called sensitization or hyperalgesia, is mediated by a variety of proinflammatory factors, including bradykinin, ATP and NGF, which cause sensitization to noxious heat stimuli by enhancing the membrane current carried by the heat- and capsaicin-gated ion channel, TRPV1. Several different mechanisms for sensitization of TRPV1 have been proposed. Here we show that NGF, acting on the TrkA receptor, activates a signalling pathway in which PI3 kinase plays a crucial early role, with Src kinase as the downstream element which binds to and phosphorylates TRPV1. Phosphorylation of TRPV1 at a single tyrosine residue, Y200, followed by insertion of TRPV1 channels into the surface membrane, explains most of the rapid sensitizing actions of NGF.
| Original language | English |
|---|---|
| Pages (from-to) | 4211-23 |
| Number of pages | 13 |
| Journal | EMBO Journal |
| Volume | 24 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - 21 Dec 2005 |
Keywords
- Amino Acid Sequence
- Animals
- Calcium
- Capsaicin
- Cell Line
- Cells, Cultured
- DNA
- DNA, Complementary
- Electrophysiology
- Gene Expression Regulation
- Glutathione Transferase
- Hot Temperature
- Humans
- Immunoblotting
- Immunohistochemistry
- Ion Channels
- Mice
- Models, Biological
- Molecular Sequence Data
- Mutation
- Nerve Growth Factor
- Neurons
- Phosphatidylinositol 3-Kinases
- Phosphorylation
- Plasmids
- Protein Binding
- Receptor, trkA
- Recombinant Fusion Proteins
- Sequence Homology, Amino Acid
- Signal Transduction
- Sodium
- TRPV Cation Channels
- Time Factors
- Transfection
- Tyrosine
- Vanadates
- src-Family Kinases