TRPV1: Structure, Endogenous Agonists, and Mechanisms

Abstract

The Transient Receptor Potential Vanilloid 1 (TRPV1) channel is a polymodal protein with functions widely linked to the generation of pain. Several agonists of exogenous and endogenous nature have been described for this ion channel. Nonetheless, detailed mechanisms and description of binding sites have been resolved only for a few endogenous agonists. This review focuses on summarizing discoveries made in this particular field of study and highlighting the fact that studying the molecular details of activation of the channel by different agonists can shed light on biophysical traits that had not been previously demonstrated.

Remedia Sternutatoria over the Centuries: TRP Mediation

“…TRPA1 and TRPV1 channels have six transmembrane (S1–S6) polypeptide subunits, permeable to cations via a pore formed by a tetramer assembly [ 142 ]. The hydrophobic pore region is located between S5 and S6 [ 143 ]. TRPA1 and TRPV1 contain ankyrin repeat motifs at the intracellular N -terminal; however, TRPA1 possess a remarkably high number of ankyrins [ 4 ].…”

“…After interaction with residues in the S4–S5 linkers, capsaicin and resiniferatoxin twitch them away, thus opening the channel. It was found that the pore region is extremely flexible, and thus, every agonist might result in a different gating mechanism [ 143 ].…”

How do Uremic Toxins Affect the Endothelium?

“…In contrast, ROS are related to the transduction of intracellular signals involved in a spectrum of biological processes [ 47 ]. ROS and their metabolites are involved in the activation of ions channel, such as transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1), which are subfamilies of the transient receptor potential (TRP) channels [ 48 , 49 , 50 ]. Both TRPV1 and TRPA1 are involved in vascular tone and endothelial cell function regulation under physiological conditions [ 48 , 49 ].…”

“…ROS and their metabolites are involved in the activation of ions channel, such as transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1), which are subfamilies of the transient receptor potential (TRP) channels [ 48 , 49 , 50 ]. Both TRPV1 and TRPA1 are involved in vascular tone and endothelial cell function regulation under physiological conditions [ 48 , 49 ]. Wang et al [ 51 ] demonstrated that the activation of TRPV1 can suppress the inflammatory response of endothelial cells.…”

TRP Channels Regulation of Rho GTPases in Brain Context and Diseases

“…TRPV1 was the first and most studied member of the vanilloid subfamily of TRP ion channels ( Caterina et al, 1997 ; Benítez-Angeles et al, 2020 ). TRPV1 can be activated by exogenous agonists such as capsaicin and resiniferatoxin (RTX) ( Caterina et al, 1997 ), as well as high temperature (>42°C), pH and membrane potential changes ( Caterina et al, 1997 ; Piper et al, 1999 ; Gunthorpe et al, 2000 ), mechanical forces ( Ho et al, 2014 ), ROS ( Starr et al, 2008 ), arachidonic acid ( Chu et al, 2003 ), and endocannabinoids ( Ross, 2003 ).…”