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Transient receptor potential receptor

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https://www.readbyqxmd.com/read/28346371/modulation-of-trp-channel-activity-by-hydroxylation-and-its-therapeutic-potential
#1
REVIEW
Yagnesh Nagarajan, Grigori Y Rychkov, Daniel J Peet
Two transient receptor potential (TRP) channels-TRPA1 and TRPV3-are post-translationally hydroxylated, resulting in oxygen-dependent regulation of channel activity. The enzymes responsible are the HIF prolyl hydroxylases (PHDs) and the asparaginyl hydroxylase factor inhibiting HIF (FIH). The PHDs and FIH are well characterized for their hydroxylation of the hypoxic inducible transcription factors (HIFs), mediating their hypoxic regulation. Consequently, these hydroxylases are currently being targeted therapeutically to modulate HIF activity in anemia, inflammation, and ischemic disease...
March 27, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28342781/modulation-of-neuroinflammation-the-role-and-therapeutic-potential-of-transient-receptor-potential-vanilloid-1-in-neuro-immune-axis
#2
REVIEW
Wei-Lin Kong, Yuan-Yuan Peng, Bi-Wen Peng
Transient receptor potential vanilloid type 1 channel (TRPV1), as a ligand-gated non-selective cation channel, has recently been demonstrated to have wide expression in the neuro-immune axis, where its multiple functions occur through regulation of both neuronal and non-neuronal activities. Growing evidence has suggested that TRPV1 is functionally expressed in glial cells, especially in the microglia and astrocytes. Glial cells perform immunological functions in response to pathophysiological challenges through pro-inflammatory or anti-inflammatory cytokines and chemokines in which TRPV1 is involved...
March 22, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28341789/met-tyrosine-kinase-inhibition-enhances-the-antitumor-efficacy-of-an-hgf-antibody
#3
Pamela J Farrell, Jennifer Matuszkiewicz, Deepika Balakrishna, Shweta Pandya, Mark S Hixon, Ruhi Kamran, Shaosong Chu, J David Lawson, Kengo Okada, Akira Hori, Akio Mizutani, Hidehisa Iwata, Ron de Jong, Barbara Hibner, Patrick Vincent
Receptor tyrosine kinase therapies have proven to be efficacious in specific cancer patient populations, however, a significant limitation of tyrosine kinase inhibitor (TKI) treatment is the emergence of resistance mechanisms leading to a transient, partial or complete lack of response. Combination therapies using agents with synergistic activity have potential to improve response and reduce acquired resistance. Chemoreagent or TKI treatment can lead to increased expression of HGF and/or MET and this effect correlates with increased metastasis and poor prognosis...
March 24, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28337975/a-chemical-chaperone-improves-muscle-function-in-mice-with-a-ryr1-mutation
#4
Chang Seok Lee, Amy D Hanna, Hui Wang, Adan Dagnino-Acosta, Aditya D Joshi, Mark Knoblauch, Yan Xia, Dimitra K Georgiou, Jianjun Xu, Cheng Long, Hisayuki Amano, Corey Reynolds, Keke Dong, John C Martin, William R Lagor, George G Rodney, Ergun Sahin, Caroline Sewry, Susan L Hamilton
Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca(2+) release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show that the I4895T mutation in RyR1 decreases the amplitude of the sarcoplasmic reticulum (SR) Ca(2+) transient, resting cytosolic Ca(2+) levels, muscle triadin content and calsequestrin (CSQ) localization to the junctional SR, and increases endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and mitochondrial ROS production...
March 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28337884/neurochemical-effects-of-photobiostimulation-in-the-trigeminal-ganglion-after-inferior-alveolar-nerve-injury
#5
D O Martins, F M Santos, L R G Britto, J B D Lemos, M Chacur
Orofacial pain is associated with peripheral and central sensitization of trigeminal nociceptive neurons. Nerve injury results in release of chemical mediators that contribute to persistent pain conditions. The activation of the transient receptor potential vanilloid 1 (TRPV1), promotes release of calcitonin gene-related peptide (CGRP) and substance P (SP) from trigeminal nerve terminals. CGRP and SP contribute to the development of peripheral hyperalgesia. The expression of SP and CGRP by primary afferent neurons is rapidly increased in response to peripheral inflammation...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337838/the-selective-metabotropic-glutamate-receptor-5-antagonist-mavoglurant-afq056-reduces-the-incidence-of-reflux-episodes-in-dogs-and-patients-with-moderate-to-severe-gastroesophageal-reflux-disease
#6
M-L Rouzade-Dominguez, N Pezous, O J David, R Tutuian, S Bruley des Varannes, J Tack, P Malfertheiner, H-D Allescher, M Ufer, A Rühl
BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) induced by gastric distension are modulated by the metabotropic glutamate receptor 5 (mGluR5) that influences the vagal reflex loop. We therefore aimed to examine the effects of the selective mGluR5 antagonist mavoglurant (AFQ056) on the number of TLESRs in dogs and reflux episodes in patients with gastroesophageal reflux disease (GERD). METHODS: In a dog model, the number of meal-induced TLESRs was determined after intravenous (0...
March 23, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28337131/changes-in-neuronal-oscillations-accompany-the-loss-of-hippocampal-ltp-that-occurs-in-an-animal-model-of-psychosis
#7
Alexander N Kalweit, Bezhad Amanpour-Gharaei, Jens Colitti-Klausnitzer, Denise Manahan-Vaughan
The first-episode of psychosis is followed by a transient time-window of ca. 60 days during which therapeutic interventions have a higher likelihood of being effective than interventions that are started with a greater latency. This suggests that, in the immediate time-period after first-episode psychosis, functional changes occur in the brain that render it increasingly resistant to intervention. The precise mechanistic nature of these changes is unclear, but at the cognitive level, sensory and hippocampus-based dysfunctions become increasingly manifest...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28336810/role-of-transient-receptor-potential-vanilloid-1-trpv1-in-the-modulation-of-airway-smooth-muscle-tone-and-calcium-handling
#8
Gene T Yocum, Jun Chen, Christine H Choi, Elizabeth A Townsend, Yi Zhang, Dingbang Xu, Xiao Wen Fu, Michael J Sanderson, Charles W Emala
Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on airway nerve fibers that modulates afferent signals resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close association with sarco/endoplasmic reticulum Ca2+ ATPase 2...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28336323/m1-muscarinic-activation-induces-long-lasting-increase-in-intrinsic-excitability-of-striatal-projection-neurons
#9
Xiaohui Lv, Jonathan W Dickerson, Jerri M Rook, Craig W Lindsley, P Jeffrey Conn, Zixiu Xiang
The dorsolateral striatum is critically involved in movement control and motor learning. Striatal function is regulated by a variety of neuromodulators including acetylcholine. Previous studies have shown that cholinergic activation excites striatal principal projection neurons, medium spiny neurons (MSNs), and this action is mediated by muscarinic acetylcholine subtype 1 receptors (M1) through modulating multiple potassium channels. In the present study, we used electrophysiology techniques in conjunction with optogenetic and pharmacological tools to determine the long-term effects of striatal cholinergic activation on MSN intrinsic excitability...
March 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28334377/lrit3-differentially-affects-connectivity-and-synaptic-transmission-of-cones-to-on-and-off-bipolar-cells
#10
Marion Neuillé, Yan Cao, Romain Caplette, Debbie Guerrero-Given, Connon Thomas, Naomi Kamasawa, José-Alain Sahel, Christian P Hamel, Isabelle Audo, Serge Picaud, Kirill A Martemyanov, Christina Zeitz
Purpose: Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). Using a cCSNB mouse model lacking Lrit3 (nob6), we recently have shown that LRIT3 has a role in the correct localization of TRPM1 (transient receptor potential melastatin 1) to the dendritic tips of ON-bipolar cells (BCs), contacting both rod and cone photoreceptors. Furthermore, postsynaptic clustering of other mGluR6 cascade components is selectively eliminated at the dendritic tips of cone ON-BCs...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28333380/smooth-muscle-ion-channels-and-regulation-of-vascular-tone-in-resistance-arteries-and-arterioles
#11
Nathan R Tykocki, Erika M Boerman, William F Jackson
Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body's tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333079/marine-cyclic-guanidine-alkaloids-monanchomycalin-b-and-urupocidin-a-act-as-inhibitors-of-trpv1-trpv2-and-trpv3-but-not-trpa1-receptors
#12
Yuliya Korolkova, Tatyana Makarieva, Kseniya Tabakmakher, Larisa Shubina, Ekaterina Kudryashova, Yaroslav Andreev, Irina Mosharova, Hyi-Seung Lee, Yeon-Ju Lee, Sergey Kozlov
Marine sponges contain a variety of low-molecular-weight compounds including guanidine alkaloids possessing different biological activities. Monanchomycalin B and urupocidin A were isolated from the marine sponge Monanchora pulchra. We found that they act as inhibitors of the TRPV1, TRPV2, and TRPV3 channels, but are inactive against the TRPA1 receptor. Monanchomycalin B is the most active among all published marine alkaloids (EC50 6.02, 2.84, and 3.25 μM for TRPV1, TRPV2, and TRPV3, correspondingly). Moreover, monanchomycalin B and urupocidin A are the first samples of marine alkaloids affecting the TRPV2 receptor...
March 23, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28332601/trpm8-in-the-negative-regulation-of-tnf%C3%AE-expression-during-cold-stress
#13
Xin-Pei Wang, Xuan Yu, Xiao-Jin Yan, Fan Lei, Yu-Shuang Chai, Jing-Fei Jiang, Zhi-Yi Yuan, Dong-Ming Xing, Li-Jun Du
Transient Receptor Potential Melastatin-8 (TRPM8) reportedly plays a fundamental role in a variety of processes including cold sensation, thermoregulation, pain transduction and tumorigenesis. However, the role of TRPM8 in inflammation under cold conditions is not well known. Since cooling allows the convergence of primary injury and injury-induced inflammation, we hypothesized that the mechanism of the protective effects of cooling might be related to TRPM8. We therefore investigated the involvement of TRPM8 activation in the regulation of inflammatory cytokines...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332266/11-12-epoxyeicosatrienoic-acid-induces-vasodilator-response-in-the-rat-perfused-mesenteric-vasculature
#14
S M Bihzad, M H M Yousif
Epoxyeicosatrienoic acids (EETs) are endogenous ligands that undergo hydrolysis by soluble epoxide hydrolase (sEH). The responses of 11, 12-EET in comparison with other vasodilator agonists including carbachol and sodium nitroprusside (SNP) were investigated. The effect of 1-cyclohexyl-3-dodecyl urea (CDU), a sEH, was tested on the vasodilator effect induced by 11, 12-EET in the perfused mesenteric beds isolated from normo-glycaemic and type-1 STZ-diabetic rats. In the perfused mesenteric beds of control and diabetic animals, 11, 12-EET produced vasodilation in a dose-dependent manner...
January 2017: Autonomic & Autacoid Pharmacology
https://www.readbyqxmd.com/read/28332202/calcium-signalling-silencing-in-atrial-fibrillation
#15
Maura Greiser
Sub-cellular calcium signalling silencing is a novel and distinct cellular and molecular adaptive response to rapid cardiac activation. Calcium signalling silencing develops during short-term sustained rapid atrial activation as seen clinically during paroxysmal atrial fibrillation (AF). It is the first 'anti-arrhythmic' adaptive response in the setting of AF and appears to counteract the maladaptive changes that lead to intracellular Ca(2+) signalling instability and Ca(2+) based arrhythmogenicity. Calcium signalling silencing results in a failed propagation of the [Ca(2+) ]i signal to the myocyte centre in both patients with AF and in a rabbit model...
March 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28331185/the-role-of-angiotensin-ii-in-glomerular-volume-dynamics-and-podocyte-calcium-handling
#16
Daria V Ilatovskaya, Oleg Palygin, Vladislav Levchenko, Bradley T Endres, Alexander Staruschenko
Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca(2+) flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II-dependent stimulation of Ca(2+) influx in the podocytes is precluded by blocking either AT1 or AT2 receptors (ATRs)...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326944/fatty-acid-binding-protein-inhibition-produces-analgesic-effects-through-peripheral-and-central-mechanisms
#17
Xiaoxue Peng, Keith Studholme, Martha P Kanjiya, Jennifer Luk, Diane Bogdan, Matthew W Elmes, Gregory Carbonetti, Simon Tong, Yu-Han Gary Teng, Robert C Rizzo, Huilin Li, Dale G Deutsch, Iwao Ojima, Mario J Rebecchi, Michelino Puopolo, Martin Kaczocha
Background Fatty-acid-binding proteins (FABPs) are intracellular carriers for endocannabinoids, N-acylethanolamines, and related lipids. Previous work indicates that systemically administered FABP5 inhibitors produce analgesia in models of inflammatory pain. It is currently not known whether FABP inhibitors exert their effects through peripheral or central mechanisms. Here, we examined FABP5 distribution in dorsal root ganglia and spinal cord and examined the analgesic effects of peripherally and centrally administered FABP5 inhibitors...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28326039/estrone-sulfate-transport-and-steroid-sulfatase-activity-in-colorectal-cancer-implications-for-hormone-replacement-therapy
#18
Lorna C Gilligan, Ali Gondal, Vivien Tang, Maryam T Hussain, Anastasia Arvaniti, Anne-Marie Hewitt, Paul A Foster
Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E1S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E1S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E1S transport in intracellular STS substrate availability...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#19
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Yin Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters but understanding of these channels remains inadequate. Here we focus on Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested including in epilepsy, innate fear, pain and cardiac remodeling but limitations in tools to probe these channels have restricted progress...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28324760/trpv1-agonism-inhibits-endothelial-cell-inflammation-via-activation-of-enos-no-pathway
#20
Youping Wang, Lin Cui, Hui Xu, Suxiao Liu, Feiyun Zhu, Fengna Yan, Si Shen, Mingjun Zhu
BACKGROUND AND AIMS: Transient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca(2+)-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation...
March 10, 2017: Atherosclerosis
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