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https://www.readbyqxmd.com/read/29164310/relevance-of-trpa1-and-trpm8-channels-as-vascular-sensors-of-cold-in-the-cutaneous-microvasculature
#1
REVIEW
Y Pan, D Thapa, L Baldissera, F Argunhan, A A Aubdool, S D Brain
Cold exposure is directly related to skin conditions, such as frostbite. This is due to the cold exposure inducing a vasoconstriction to reduce cutaneous blood flow and protect against heat loss. However, a long-term constriction will cause ischaemia and potentially irreversible damage. We have developed techniques to elucidate the mechanisms of the vascular cold response. We focused on two ligand-gated transient receptor potential (TRP) channels, namely, the established "cold sensors" TRP ankyrin 1 (TRPA1) and TRP melastin (TRPM8)...
November 21, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29138055/merkel-cells-sense-cooling-with-trpm8-channels
#2
Valentine Bouvier, Yann Roudaut, Nancy Osorio, Jean-Marc Aimonetti, Edith Ribot-Ciscar, Virginie Penalba, Thierry Merrot, Nicolas Lebonvallet, Christelle Le Gall-Ianotto, Laurent Misery, Patrick Delmas, Marcel Crest
In the skin, Merkel cells (MCs) connect with keratinocytes and Aβ nerve fibers to form a touch receptor which functions as a slow adapting mechanoreceptor (SA1 receptor). In human and mouse MCs, we observed an increased concentration of intracellular Ca(2+) ions in response to cold temperature and transient receptor potential melastatine 8 (TRPM8) ion channel agonists. A reduction in the response to cooling and TRPM8 agonists occurred following addition of TRPM8 antagonists, as well as in TRPM8 knockout mice...
November 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29130364/fluorescent-labeling-and-2-photon-imaging-of-mouse-tooth-pulp-nociceptors
#3
A Kadala, P Sotelo-Hitschfeld, Z Ahmad, P Tripal, B Schmid, A Mueller, L Bernal, Z Winter, S Brauchi, U Lohbauer, K Messlinger, J K Lennerz, K Zimmermann
Retrograde fluorescent labeling of dental primary afferent neurons (DPANs) has been described in rats through crystalline fluorescent DiI, while in the mouse, this technique was achieved with only Fluoro-Gold, a neurotoxic fluorescent dye with membrane penetration characteristics superior to the carbocyanine dyes. We reevaluated this technique in the rat with the aim to transfer it to the mouse because comprehensive physiologic studies require access to the mouse as a model organism. Using conventional immunohistochemistry, we assessed in rats and mice the speed of axonal dye transport from the application site to the trigeminal ganglion, the numbers of stained DPANs, and the fluorescence intensity via 1) conventional crystalline DiI and 2) a novel DiI formulation with improved penetration properties and staining efficiency...
November 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29115578/characterization-of-prostate-cancer-cell-progression-in-zebrafish-xenograft-model
#4
Wei Xu, Brittany A Foster, Mackenzie Richards, Kenneth R Bondioli, Girish Shah, Christopher C Green
Early diagnosis of prostate cancer (PCa) is critical for the application of efficient treatment to PCa patients. However, the majority of PCas remains indolent from several months to several years before malignancy. Current diagnosis methods have limitations in their reliability and are inefficient in time cost. Thus, an efficient in vivo PCa cell xenograft model is highly desired for diagnostic studies in PCas. In the present study we present a standardized procedure to create a PCa cell xenograft model using zebrafish (Danio rerio) as the host...
November 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29114087/the-cooling-compound-icilin-attenuates-autoimmune-neuroinflammation-through-modulation-of-the-t-cell-response
#5
Benjamin W Ewanchuk, Euan R O Allan, Amy L Warren, Rithwik Ramachandran, Robin M Yates
The synthetic supercooling drug, icilin, and its primary receptor target, the cation channel transient receptor potential (TRP) melastatin-8 (TRPM8), have been described as potent negative regulators of inflammation in the colon. The aim of this study was to determine whether the anti-inflammatory action of icilin could potentially be used to treat autoimmune neuroinflammatory disorders, such as multiple sclerosis (MS). During experimental autoimmune encephalomyelitis (EAE)-a CD4(+) T cell-driven murine model of MS-we found that both wild-type (WT) and TRPM8-deficient EAE mice were protected from disease progression during icilin treatment, as evidenced by delays in clinical onset and reductions in neuroinflammation...
November 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29112508/estrogen-modulates-corneal-nociception-and-maintains-corneal-homeostasis-in-rat-eye
#6
Vinod Kumar, Vishma Pratap Sur, Rajdeep Guha, Aditya Konar, Sarbani Hazra
PURPOSE: To evaluate the role of estrogen in corneal nociception, its influence on lacrimal secretion, and development of dry eye. METHODS: Ovariectomy was performed in normal healthy female rats (OVX). Estrogen replacement was performed in a population of these rats (OVX+E). Tests for dry eye and corneal sensitivity were performed and compared with rats in proestrus (PRO) as controls. Gene expression of neuropeptides such as substance P, calcitonin gene receptor-like protein (CGRP), estrogen receptor α, TRPV1, and TRPM8 was evaluated in the cornea and trigeminal ganglion...
November 6, 2017: Cornea
https://www.readbyqxmd.com/read/29102663/signaling-pathways-relevant-to-nerve-growth-factor-induced-upregulation-of-transient-receptor-potential-m8-expression
#7
Yohei Kayama, Mamoru Shibata, Tsubasa Takizawa, Keiji Ibata, Jin Nakahara, Toshihiko Shimizu, Haruki Toriumi, Michisuke Yuzaki, Norihiro Suzuki
Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel that primarily detects the innocuous cold. In pathological conditions, TRPM8 plays a role in the development of cold hyperalgesia/allodynia. Nerve growth factor (NGF) is an important mediator involved in various pain disorders. In the present study, the NGF-TrkA pathway increased TRPM8 expression by stabilizing TRPM8 mRNA through the actions of phosphatidylinositol 3-kinase and p38 MAP kinase. Moreover, c-Jun N-terminal kinase and Src tyrosine kinase were identified as a positive and negative regulator of TRPM8 expression, respectively, via post-transcriptional mechanisms independent of mRNA stabilization...
November 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/29099043/involvement-of-opioid-system-trpm8-and-asic-receptors-in-antinociceptive-effect-of-arrabidaea-brachypoda-dc-bureau
#8
Vinícius Peixoto Rodrigues, Cláudia Quintino da Rocha, Larissa Lucena Périco, Raquel de Cássia Dos Santos, Rie Ohara, Catarine Massucato Nishijima, Emerson Ferreira Queiroz, Jean-Luc Wolfender, Lúcia Regina Machado da Rocha, Adair Roberto Soares Santos, Wagner Vilegas, Clélia Akiko Hiruma-Lima
Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29080031/ikd-current-in-cold-transduction-and-damage-triggered-cold-hypersensitivity
#9
Alejandro González, Gaspar Herrera, Gonzalo Ugarte, Carlos Restrepo, Ricardo Piña, María Pertusa, Patricio Orio, Rodolfo Madrid
In primary sensory neurons of the spinal and trigeminal somatosensory system, cold-sensitivity is strongly dependent on the functional balance between TRPM8 channels, the main molecular entity responsible for the cold-activated excitatory current, and Shaker-like Kv1.1-1.2 potassium channels, the molecular counterpart underlying the excitability brake current IKD. This slow-inactivating outward K(+) current reduces the excitability of cold thermoreceptor neurons increasing their thermal threshold, and prevents unspecific activation by cold of neurons of other somatosensory modalities...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29078169/menthol-evokes-ca-2-signals-and-induces-oxidative-stress-independently-of-the-presence-of-trpm8-menthol-receptor-in-cancer-cells
#10
Mustafa Nazıroğlu, Walter Blum, Katalin Jósvay, Bilal Çiğ, Thomas Henzi, Zoltán Oláh, Csaba Vizler, Beat Schwaller, László Pecze
Menthol is a naturally occurring monoterpene alcohol possessing remarkable biological properties including antipruritic, analgesic, antiseptic, anti-inflammatory and cooling effects. Here, we examined the menthol-evoked Ca(2+) signals in breast and prostate cancer cell lines. The effect of menthol (50-500µM) was predicted to be mediated by the transient receptor potential ion channel melastatin subtype 8 (TRPM8). However, the intensity of menthol-evoked Ca(2+) signals did not correlate with the expression levels of TRPM8 in breast and prostate cancer cells indicating a TRPM8-independent signaling pathway...
October 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/29054764/trpm8-activation-improves-energy-expenditure-in-skeletal-muscle-and-exercise-endurance-in-mice
#11
Chen Li, Jia Li, Xiujuan Xiong, Ying Liu, Yanxia Lv, Shanshan Qin, Dandan Liu, Ronghua Wei, Xuzhi Ruan, Jingxuan Zhang, Liang Xu, Xuanbin Wang, Jicheng Chen, Yonghong Zhang, Lanlan Zheng
Skeletal muscle serving as the major organ is responsible for energy expenditure and exercise endurance, which directly influence cardiometabolic risk factors. Transient receptor potential melastatin 8 (TRPM8), a Ca(2+)-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the energy metabolism of adipocytes. However, the involvement of TRPM8 in the energy metabolism of skeletal muscle remains unexplored...
October 17, 2017: Gene
https://www.readbyqxmd.com/read/29054683/the-anthelminthic-drug-praziquantel-is-a-selective-agonist-of-the-sensory-transient-receptor-potential-melastatin-type-8-channel
#12
Ramona-Madalina Babes, Tudor Selescu, Dan Domocos, Alexandru Babes
Praziquantel is the most effective anthelminthic drug for the treatment of schistosomiasis, an infectious disease caused by the platyhelminth Schistosoma mansoni. While praziquantel is known to trigger calcium influx into schisostomes, followed by spastic paralysis of the worms and tegumental disruption, the mechanism of action of the drug is not completely understood. Although relatively well tolerated, praziquantel has been reported to cause mild adverse effects, including nausea, abdominal pain and headaches...
October 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29038158/activation-of-human-transient-receptor-potential-melastatin-8-trpm8-by-calcium-rich-particulate-materials-and-effects-on-human-lung-cells
#13
John G Lamb, Erin G Romero, Zhenyu Lu, Seychelle K Marcus, Hannah C Peterson, John M Veranth, Cassandra E Deering-Rice, Christopher A Reilly
To better understand how adverse health effects are caused by particulate materials, and to develop preventative measures, it is important to identify the properties of particles and proteins that link exposure with specific biological outcomes. Coal fly ash (CFA) is a by-product of coal combustion that can affect human health. Here we show that human transient receptor potential melastatin-8 (TRPM8) and an N-terminally truncated TRPM8 variant (TRPM8-Δ801) are activated by CFA and calcium-rich nanoparticles and/or soluble salts within CFA...
October 16, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29034580/selective-inhibition-of-trpm2-channel-by-two-novel-synthesized-adpr-analogues
#14
Xiao Luo, Meng Li, Kaiyu Zhan, Wei Yang, Lihe Zhang, KeWei Wang, Peilin Yu, Liangren Zhang
Transient receptor potential melastatin-2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover novel and selective TRPM2 inhibitors, a series of adenosine 5'-diphosphoribose (ADPR) analogues were synthesized and their activities and selectivity were evaluated. Whole-cell patch clamp recordings were employed for screen and evaluation of synthesized compounds...
October 15, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28985244/menthol-induced-cutaneous-vasodilation-is-preserved-in-essential-hypertensive-men-and-women
#15
Daniel H Craighead, Lacy M Alexander
BACKGROUND: Menthol is a selective transient receptor potential melastatin 8 (TRPM8) channel agonist that induces cutaneous vasodilation in young, normotensive men and women through nitric oxide synthase (NOS)-, endothelium-derived hyperpolarizing factor (EDHF)-, and sensory nerve-mediated mechanisms. Microvascular dysfunction is present in essential hypertension and whether menthol induces vasodilation is men and women with essential hypertension is equivocal. METHODS: Four intradermal microdialysis fibers were placed in the forearm of 9 essential hypertensive and 10 age-matched normotensive control subjects...
November 6, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28952330/genome-wide-association-study-identifies-novel-susceptibility-loci-for-migraine-in-han-chinese-resided-in-taiwan
#16
Shih-Pin Chen, Jong-Ling Fuh, Ming-Yi Chung, Ying-Chao Lin, Yi-Chu Liao, Yen-Feng Wang, Chia-Lin Hsu, Ueng-Cheng Yang, Ming-Wei Lin, Jen-Jie Chiou, Po-Jen Wang, Ping-Kun Chen, Pi-Chuan Fan, Jer-Yuan Wu, Yuan-Tsong Chen, Lung-Sen Kao, Cathy Shen-Jang Fann, Shuu-Jiun Wang
Background Susceptibility genes for migraine, despite it being a highly prevalent and disabling neurological disorder, have not been analyzed in Asians by genome-wide association study (GWAS). Methods We conducted a two-stage case-control GWAS to identify susceptibility genes for migraine without aura in Han Chinese residing in Taiwan. In the discovery stage, we genotyped 1005 clinic-based Taiwanese migraine patients and 1053 population-based sex-matched controls using Axiom Genome-Wide CHB Array. In the replication stage, we genotyped 27 single-nucleotide polymorphisms with p < 10(-4) in 1120 clinic-based migraine patients and 604 sex-matched normal controls by using Sequenom...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28952176/pilot-evaluation-of-the-antipruritic-efficacy-of-a-topical-transient-receptor-potential-melastatin-subfamily-8-trpm8-agonist-in-dogs-with-atopic-dermatitis-and-pedal-pruritus
#17
Chie Tamamoto-Mochizuki, K Marcia Murphy, Thierry Olivry
BACKGROUND: Atopic dermatitis (AD) requires a multimodal therapy and there is a need for effective adjunctive interventions. TRPM8 agonists are known to alleviate pruritus by inducing cooling. OBJECTIVES: To evaluate the efficacy of a novel TRPM8 agonist, 1-diisopropylphosphorylheptane (Cryosim-1), in atopic dogs. ANIMALS: Nine client owned dogs with moderate to severe pedal pruritus associated with nonseasonal AD. METHODS: This was a prospective, randomized, double-blinded, intraindividual, placebo-controlled study...
September 26, 2017: Veterinary Dermatology
https://www.readbyqxmd.com/read/28945977/trp-channels-as-potential-drug-targets
#18
Magdalene M Moran
The transient receptor potential (TRP) superfamily of channels comprises a diverse group of cation channels. Four TRP channel subunits coassemble to form functional homo- or heterotetramers that pass sodium, calcium, or both in the inward direction. Modulating TRP channel activity provides an important way to impact cellular function by regulating both membrane excitability and intracellular calcium levels. The import of these channels is underscored by the number of genetic diseases caused when they are mutated: Skeletal, skin, sensory, ocular, cardiac, and neuronal disturbances all arise from aberrant TRP function...
September 25, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28943398/cold-sensing-trpm8-channel-participates-in-circadian-control-of-the-brown-adipose-tissue
#19
Maria Nathália Moraes, Leonardo Vinicius Monteiro de Assis, Felipe Dos Santos Henriques, Miguel Luiz Batista, Ali D Güler, Ana Maria de Lauro Castrucci
Transient receptor potential (TRP) channels are known to regulate energy metabolism, and TRPM8 has become an interesting player in this context. Here we demonstrate the role of the cold sensor TRPM8 in the regulation of clock gene and clock controlled genes in brown adipose tissue (BAT). We investigated TrpM8 temporal profile in the eyes, suprachiasmatic nucleus and BAT; only BAT showed temporal variation of TrpM8 transcripts. Eyes from mice lacking TRPM8 lost the temporal profile of Per1 in LD cycle. This alteration in the ocular circadian physiology may explain the delay in the onset of locomotor activity in response to light pulse, as compared to wild type animals (WT)...
December 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28933582/dynamic-sensitivity-of-corneal-trpm8-receptors-to-menthol-instillation-in-dry-eye-versus-normal-subjects
#20
Peter Corcoran, David A Hollander, George W Ousler, Endri Angjeli, David Rimmer, Keith Lane, Mark B Abelson
PURPOSE: To assess the sensitivity of corneal cold receptors to a known transient receptor potential melastatin 8 (TRPM8) agonist, menthol, in dry eye and normals, and to determine whether factors such as disease duration or age affect responses. METHODS: Dry eye disease (DED) (N = 33) and normal (N = 15) subjects were randomly assigned to receive Rohto(®) Hydra (0.01% menthol) or Systane(®) Ultra treatments (OU) in a prospective, double-blind, crossover study...
November 2017: Journal of Ocular Pharmacology and Therapeutics
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