RT Journal Article
SR Electronic
T1 Structure-Driven Pharmacology of Transient Receptor Potential Channel Vanilloid 1
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 300
OP 308
DO 10.1124/mol.116.104430
VO 90
IS 3
A1 Ignacio Díaz-Franulic
A1 Javier Caceres-Molina
A1 Romina V. Sepulveda
A1 Fernando Gonzalez-Nilo
A1 Ramon Latorre
YR 2016
UL http://molpharm.aspetjournals.org/content/90/3/300.abstract
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.