Transient receptor potential channels as novel drug targets in respiratory diseases

Curr Opin Investig Drugs. 2010 May;11(5):535-42.

Abstract

A subpopulation of nociceptive primary sensory neurons expresses six different transient receptor potential (TRP) ion channels of the vanilloid (V1, V2, V3 and V4), melastatin (M8) and ankyrin (A1) subtypes. TRPV1 mediates the tussive action of capsaicin, which is widely used in cough provocation studies. The upregulation of TRPV1 expression and function has been reported in asthma and other inflammatory conditions. TRPA1 is targeted by a series of byproducts of oxidative and nitrative stress, including acrolein, 4-hydroxy-2-nonenal and hydrogen peroxide. Proinflammatory neuropeptides are released from nociceptive nerve terminals after TRPV1/TRPA1 stimulation, thereby causing airway neurogenic inflammation. In addition, the early inflammatory response to cigarette smoke is mediated entirely by neuronal TRPA1. TRPV1 and TRPA1 antagonists may therefore represent potential antitussive and anti-inflammatory therapeutics for respiratory airway diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Drug Design*
  • Humans
  • Neuropeptides / metabolism
  • Respiratory System / drug effects*
  • Respiratory System / immunology
  • Respiratory System / innervation
  • Respiratory System / metabolism
  • Respiratory Tract Diseases / drug therapy*
  • Respiratory Tract Diseases / immunology
  • Respiratory Tract Diseases / metabolism
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / immunology
  • Sensory Receptor Cells / metabolism
  • Transient Receptor Potential Channels / antagonists & inhibitors*
  • Transient Receptor Potential Channels / biosynthesis

Substances

  • Anti-Inflammatory Agents
  • Neuropeptides
  • Transient Receptor Potential Channels