The Endocannabinoid Peptide RVD-Hemopressin Is a TRPV1 Channel Blocker

• Published in: Biomolecules (Basel, Switzerland) Vol. 14; no. 9; p. 1134
• Main Authors: Suárez-Suárez, Constanza, González-Pérez, Sebastián, Márquez-Miranda, Valeria, Araya-Duran, Ingrid, Vidal-Beltrán, Isabel, Vergara, Sebastián, Carvacho, Ingrid, Hinostroza, Fernando
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08-09-2024; MDPI
• Subjects: Antibodies; Behavior; Calcium - metabolism; Calcium currents; Calcium imaging; Calcium influx; Calcium signalling; Cannabinoid CB1 receptors; Cannabinoid CB2 receptors; Capsaicin receptors; Endocannabinoids - chemistry; Endocannabinoids - metabolism; Endocannabinoids - pharmacology; Glucose; HEK293 Cells; Hemoglobins; Humans; Hydrogen; Hydrogen bonding; Hyperalgesia; Hypothalamus; Ion currents; Microscopy; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; molecular dynamics simulations; Neuroimaging; Neurons; Neuropeptides; Neurotransmission; patch-clamp electrophysiology; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Peptides; Receptor mechanisms; RVD-hemopressin; Simulation methods; Software; Spinal cord; Temperature; Transient receptor potential proteins; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - metabolism; TRPV1 channel; Chile; Massachusetts; Ann Arbor Michigan; United States > US; molecular dynamics simulations; patch-clamp electrophysiology; TRPV1 channel; RVD-hemopressin; calcium imaging
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14091134

Neurotransmission is critical for brain function, allowing neurons to communicate through neurotransmitters and neuropeptides. RVD-hemopressin (RVD-Hp), a novel peptide identified in noradrenergic neurons, modulates cannabinoid receptors CB1 and CB2. Unlike hemopressin (Hp), which induces anxiogenic behaviors via transient receptor potential vanilloid 1 (TRPV1) activation, RVD-Hp counteracts these effects, suggesting that it may block TRPV1. This study investigates RVD-Hp's role as a TRPV1 channel blocker using HEK293 cells expressing TRPV1-GFP. Calcium imaging and patch-clamp recordings demonstrated that RVD-Hp reduces TRPV1-mediated calcium influx and TRPV1 ion currents. Molecular docking and dynamics simulations indicated that RVD-Hp interacts with TRPV1's selectivity filter, forming stable hydrogen bonds and van der Waals contacts, thus preventing ion permeation. These findings highlight RVD-Hp's potential as a therapeutic agent for conditions involving TRPV1 activation, such as pain and anxiety.