Dissecting TRPV1: lessons to be learned?

Channels (Austin). May-Jun 2011;5(3):201-4. doi: 10.4161/chan.5.3.16291. Epub 2011 May 1.

Abstract

The transient receptor potential channel TRPV1 is a polymodal nociceptor. It is primarily expressed in dorsal root ganglia and peripheral sensory nerve endings, and to a much lesser extent, in the central nervous system. It has also been implicated in the functional properties of e.g. urinary and bronchial epithelia. TRPV1 has long been under intensive investigation by the pharmaceutical industry as a candidate drug target especially for pain conditions. This review summarizes the current knowledge of the molecular determinants of TRPV1 channel activation by heat, protons and capsaicin. Newly discovered heat and proton activation sites within the pore domain are discussed as well as potential consequences for drug discovery. Polymodal TRPV1 antagonists were found to cause hyperthermia in a species-dependent manner in-vivo, hence the discovery of euthermic compounds with an appropriate modality selectivity profile will be crucial for TRPV1's future as a drug target.

Publication types

  • Review

MeSH terms

  • Animals
  • Capsaicin / pharmacology
  • Drug Delivery Systems
  • Fever / genetics
  • Fever / metabolism
  • Ganglia, Spinal / metabolism*
  • Hot Temperature
  • Nociceptors / metabolism*
  • Pain / drug therapy
  • Pain / metabolism
  • Protons
  • Respiratory Mucosa / metabolism*
  • Species Specificity
  • TRPV Cation Channels / agonists
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Urothelium / metabolism*

Substances

  • Protons
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Capsaicin