Beyond Hot and Spicy: TRPV Channels and their Pharmacological Modulation

Cell Physiol Biochem. 2021 May 28;55(S3):108-130. doi: 10.33594/000000358.


Transient receptor potential vanilloid (TRPV) channels are part of the TRP channel superfamily and named after the first identified member TRPV1, that is sensitive to the vanillylamide capsaicin. Their overall structure is similar to the structure of voltage gated potassium channels (Kv) built up as homotetramers from subunits with six transmembrane helices (S1-S6). Six TRPV channel subtypes (TRPV1-6) are known, that can be subdivided into the thermoTRPV (TRPV1-4) and the Ca2+-selective TRPV channels (TRPV5, TRPV6). Contrary to Kv channels, TRPV channels are not primary voltage gated. All six channels have distinct properties and react to several endogenous ligands as well as different gating stimuli such as heat, pH, mechanical stress, or osmotic changes. Their physiological functions are highly diverse and subtype as well as tissue specific. In many tissues they serve as sensors for different pain stimuli (heat, pressure, pH) and contribute to the homeostasis of electrolytes, the maintenance of barrier functions and the development of macrophages. Due to their fundamental role in manifold physiological and pathophysiological processes, TRPV channels are promising targets for drug development. However, drugs targeting specific TRPV channels, that are suitable for drug therapy, are rare. Moreover, selective and potent compounds for further research at TRPV channels are often lacking. In this review different aspects of the structure, the different gating stimuli, the expression pattern, the physiological and pathophysiological roles as well as the modulating mechanisms of synthetic, natural and endogenous ligands are summarized.

Keywords: TRPV; Molecular pharmacology; Capsaicin; Ion channel modulation; Medicinal chemistry.

Publication types

  • Review

MeSH terms

  • Analgesics / chemistry
  • Analgesics / classification
  • Analgesics / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / classification
  • Antineoplastic Agents / pharmacology*
  • Binding Sites
  • Brain / cytology
  • Brain / drug effects
  • Brain / metabolism
  • Humans
  • Immunologic Factors / chemistry
  • Immunologic Factors / classification
  • Immunologic Factors / pharmacology*
  • Ion Channel Gating / drug effects
  • Ligands
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism
  • Membrane Transport Modulators / chemistry
  • Membrane Transport Modulators / classification
  • Membrane Transport Modulators / pharmacology*
  • Models, Molecular
  • Organ Specificity
  • Protein Binding
  • Protein Isoforms / agonists
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / classification
  • Protein Isoforms / metabolism
  • Protein Structure, Secondary
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / metabolism
  • TRPV Cation Channels / agonists
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / classification
  • TRPV Cation Channels / metabolism*


  • Analgesics
  • Antineoplastic Agents
  • Immunologic Factors
  • Ligands
  • Membrane Transport Modulators
  • Protein Isoforms
  • TRPV Cation Channels