14,15-epoxyeicosatrienoic acid (14,15-EET) is implicated in regulating physiological functions of endothelial cells (ECs), yet the potential molecular mechanisms underlying the beneficial effects in ECs are not fully understood. In this study, we investigated whether transient receptor potential vanilloid receptor type 1 (TRPV1) is involved in 14,15-EET-mediated Ca(2+) influx, nitric oxide (NO)...

TRPV1 (transient receptor potential vanilloid receptor subtype 1) is a member of the TRP channel family gated by vanilloids, protons, and heat. Structurally, TRPV1 appears to be a tetramer formed by the assembly of four identical subunits around a central aqueous pore. The molecular determinants that govern its subunit oligomerization remain elusive. Here, we report the identification of a segm...

The oleyl moiety in vanilloids is important in activating vanilloid receptor 1 (TRPV1), but there was no ingredient of ginger containing the oleyl moiety in the natural form. We synthesized oleylgingerol and oleylshogaol and then evaluated their potential to activate a rat TRPV1 channel. Oleylgingerol is a stronger TRPV1 agonist than natural gingerols, but oleylshogaol is a weaker agonist than ...

An amiloride-insensitive (AI) salt taste receptor is the predominant transducer of Na+ taste in some mammalian species. Accordingly, the objective of this study was to characterize the AI-salt taste receptor. The AI-salt taste receptor in rat and mouse fungiform taste receptor cells (TRCs) was activated by the vanilloid receptor-1 (VR-1) agonists, resiniferatoxin (RTX), capsiacin (CAP) and elev...

The low extracellular pH of inflamed or ischemic tissues enhances painful sensations by sensitizing and activating the vanilloid receptor 1 (TRPV1). We report here that activation of TRPV1 results in a marked intracellular acidification in nociceptive dorsal root ganglion neurons and in a heterologous expression system. A characterization of the underlying mechanisms revealed a Ca(2+)-dependent...

Many nociceptors detect mechanical cues, but the ion channels responsible for mechanotransduction in these sensory neurons remain obscure. Using in vivo recordings and genetic dissection, we identified the DEG/ENaC protein, DEG-1, as the major mechanotransduction channel in ASH, a polymodal nociceptor in Caenorhabditis elegans. But DEG-1 is not the only mechanotransduction channel in ASH: loss ...

Background: Type 1 vanilloid receptors (TRPV1) have been described on esophageal afferent sensitive neurons. Stimulation of TRPV1 receptors with capsaicin may induce heartburn. Capsaicin is the pungent component of chili and the most extensively studied TRPV1 agonist. Objectives: To investigate the effect of esophageal stimulation with intraesophageal capsaicin administration on induction of es...

The vanilloid receptor subunit 1, or transient receptor potential vanilloid 1 (TRPV1), integrates physical and chemical stimuli in the peripheral nervous system, playing a key role in inflammatory pain. Identification of potent TRPV1 antagonists is thus an important goal of current neuropharmacology. Herein, we describe the solid-phase synthesis of a series of indole-based peptoids (N-alkylglyc...

Tracy D. Wilson-Gerwing,1 Myles V. Dmyterko,1 Douglas W. Zochodne,2 Jayne M. Johnston,1 and Valerie M. K. Verge1 1Department of Anatomy and Cell Biology, Cameco Multiple Sclerosis Neuroscience Research Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E5, and 2Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Calgary, Alberta...

The TRPV subfamily of calcium-permeable channels is widely distributed in sensory and nonsensory cells from nematodes to mammals. These channels can be variably activated by a diverse range of stimuli (osmotic/mechanical stress, noxious chemicals and heat, endogenous mediators) that often converge on the same channel. Evidence is presented that TRPV channels function as novel "molecular integra...