PT  - JOURNAL ARTICLE
AU  - Díaz-Franulic, Ignacio
AU  - Caceres-Molina, Javier
AU  - Sepulveda, Romina V.
AU  - Gonzalez-Nilo, Fernando
AU  - Latorre, Ramon
TI  - Structure-Driven Pharmacology of Transient Receptor Potential Channel Vanilloid 1
AID  - 10.1124/mol.116.104430
DP  - 2016 Sep 01
TA  - Molecular Pharmacology
PG  - 300--308
VI  - 90
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/90/3/300.short
4100  - http://molpharm.aspetjournals.org/content/90/3/300.full
SO  - Mol Pharmacol2016 Sep 01; 90
AB  - The transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor that mediates the flux of cations across the membrane in response to several stimuli, including heat, voltage, and ligands. The best known agonist of TRPV1 channels is capsaicin, the pungent component of “hot” chili peppers. In addition, peptides found in the venom of poisonous animals, along with the lipids phosphatidylinositol 4,5-biphosphate, lysophosphatidic acid, and cholesterol, bind to TRPV1 with high affinity to modulate channel gating. Here, we discuss the functional evidence regarding ligand-dependent activation of TRPV1 channels in light of structural data recently obtained by cryoelectron microscopy. This review focuses on the mechanistic insights into ligand binding and allosteric gating of TRPV1 channels and the relevance of accurate polymodal receptor biophysical characterization for drug design in novel pain therapies.