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https://www.readbyqxmd.com/read/28179555/role-of-the-excitability-brake-potassium-current-ikd-in-cold-allodynia-induced-by-chronic-peripheral-nerve-injury
#1
Alejandro González, Gonzalo Ugarte, Carlos Restrepo, Gaspar Herrera, Ricardo Piña, José Antonio Gómez-Sánchez, María Pertusa, Patricio Orio, Rodolfo Madrid
Cold allodynia is a common symptom of neuropathic and inflammatory pain following peripheral nerve injury. The mechanisms underlying this disabling sensory alteration are not entirely understood. In primary somatosensory neurons, cold-sensitivity is mainly determined by a functional counterbalance between cold-activated TRPM8 channels and Shaker-like Kv1.1-1.2 channels underlying the excitability brake current IKD Here we studied the role of IKD in damage-triggered painful hypersensitivity to innocuous cold...
February 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28138709/trpm8-downregulation-by-angiotensin-ii-in-vascular-smooth-muscle-cells-is-involved-in-hypertension
#2
Fang Huang, Min Ni, Jing-Ming Zhang, Dong-Jie Li, Fu-Ming Shen
Angiotensin II (Ang II)-induced injury of vascular smooth muscle cells (VSMCs) serves an important role in hypertension and other cardiovascular disorders. Transient receptor potential melastatin 8 (TRPM8) is a thermally‑regulated Ca2+‑permeable channel that is activated by reduced body temperature. Although several recent studies have revealed the regulatory effect of TRPM8 in vascular tone and hypertension, the precise role of TRPM8 in dysfunction of vascular smooth muscle cells (VSMCs) induced by Ang II remains elusive...
January 30, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28101241/potential-role-of-melastatin-related-transient-receptor-potential-cation-channel-subfamily-m-gene-expression-in-the-pathogenesis-of-urinary-bladder-cancer
#3
Gülay Güleç Ceylan, Ebru Etem Önalan, Tuncay Kuloğlu, Gülten Aydoğ, İbrahim Keleş, Şenol Tonyali, Cavit Ceylan
Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28066924/side-chain-flexibility-and-coupling-between-the-s4-s5-linker-and-the-trp-domain-in-thermo-sensitive-trp-channels-insights-from-protein-modeling
#4
Sergio Romero-Romero, Froylan Gómez-Lagunas, Daniel Balleza
The transient receptor potential (TRP) superfamily is subdivided into several subfamilies on the basis of sequence similarity, which is highly heterogeneous but shows a molecular architecture that resembles the one present in members of the Kv channel superfamily. Because of this diversity, they produce a large variety of channels with different gating and permeability properties. Elucidation of these particular features necessarily requires comparative studies based on structural and functional data. The present study aims to compilate, analyze, and determine, in a coherent way, the relationship between intrinsic side-chain flexibility and the allosteric coupling in members of the TRPV, TRPM, and TRPC families...
January 9, 2017: Proteins
https://www.readbyqxmd.com/read/28053885/shakuyakukanzoto-attenuates-oxaliplatin-induced-cold-dysesthesia-by-inhibiting-the-expression-of-transient-receptor-potential-melastatin-8-in-mice
#5
Tsugunobu Andoh, Shizuka Mizoguchi, Yasushi Kuraishi
Oxaliplatin-induced peripheral neuropathy characterized especially as cold dysesthesia is a major dose-limiting side effect of the drug and is very difficult to control. In the present study, we examined whether the traditional herbal formulation Shakuyakukanzoto (SKT: Sháo Yào Gān Cǎo Tāng) could relieve oxaliplatin-induced cold dysesthesia in mice. The inhibitory mechanisms were also investigated. Repetitive administration of SKT (0.1-1.0 g/kg) starting from the day after oxaliplatin injection inhibited cold dysesthesia in a dose-dependent manner...
January 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/28043013/transient-receptor-potential-melastatin-trpm-8-is-expressed-in-freshly-isolated-native-human-odontoblasts
#6
Kento Tazawa, Hideharu Ikeda, Nobuyuki Kawashima, Takashi Okiji
OBJECTIVE: Cold-sensitive ion channels, such as transient receptor potential melastatin (TRPM) 8 and transient receptor potential ankyrin (TRPA) 1, may play a crucial role in the nociceptive function of odontoblasts, whereas expression of these TRP channels in human native odontoblasts remains to be elucidated. This study aimed to analyze the expression of TRPM8 and TRPA1 in freshly isolated native human odontoblasts. DESIGN: Odontoblasts were isolated from freshly extracted healthy human teeth (n=4); after removing the inner pulp tissues from the pulp chambers, odontoblasts remaining on the dentin surface were washed out with phosphate buffered saline and collected...
December 23, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/28039451/high-throughput-proteome-analysis-reveals-targeted-trpm8-degradation-in-prostate-cancer
#7
Swapna Asuthkar, Lusine Demirkhanyan, Samuel Robert Mueting, Alejandro Cohen, Eleonora Zakharian
The Ca2+-permeable ion channel TRPM8 is a hallmark of the prostate epithelium. We recently discovered that TRPM8 is an ionotropic testosterone receptor. This finding suggested that testosterone-induced TRPM8 activity regulates Ca2+ homeostasis in the prostate epithelium. Since androgens are significantly implicated in prostate cancer development, the role of the novel testosterone receptor TRPM8 in cancer was assessed in our study. Although TRPM8 mRNA levels increase at the early prostate cancer stages, we found that it is not proportionally translated into TRPM8 protein levels...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28038937/cellular-permeation-of-large-molecules-mediated-by-trpm8-channels
#8
Daniel D McCoy, Radhika Palkar, Yuening Yang, Serra Ongun, David D McKemy
While most membrane channels are only capable of passing small ions, certain non-selective cation channels have been recently shown to have the capacity to permeate large cations. The mechanisms underlying large molecule permeation are unclear, but this property has been exploited pharmacologically to target molecules, such as nerve conduction blockers, to specific subsets of pain-sensing neurons (nociceptors) expressing the heat-gated transient receptor potential (TRP) channel TRPV1. However, it is not clear if the principal mediator of cold stimuli TRPM8 is capable of mediating the permeation large molecules across cell membranes, suggesting that TRPM8-positive nerves cannot be similarly targeted...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28025641/itraq-based-proteomics-identification-of-serum-biomarkers-of-two-chronic-hepatitis-b-subtypes-diagnosed-by-traditional-chinese-medicine
#9
Jiankun Yang, Lichao Yang, Baixue Li, Weilong Zhou, Sen Zhong, Zhenhua Zhuang, Bin Yang, Maoshan Chen, Quansheng Feng
Background. Chronic infection with hepatitis B virus (HBV) is a leading cause of cirrhosis and hepatocellular carcinoma. By traditional Chinese medicine (TCM) pattern classification, damp heat stasis in the middle-jiao (DHSM) and liver Qi stagnation and spleen deficiency (LSSD) are two most common subtypes of CHB. Results. In this study, we employed iTRAQ proteomics technology to identify potential serum protein biomarkers in 30 LSSD-CHB and 30 DHSM-CHB patients. Of the total 842 detected proteins, 273 and 345 were differentially expressed in LSSD-CHB and DHSM-CHB patients compared to healthy controls, respectively...
2016: BioMed Research International
https://www.readbyqxmd.com/read/28008282/expression-and-functionality-of-trpv1-in-breast-cancer-cells
#10
Lea V Weber, Klaudia Al-Refae, Gerhard Wölk, Gabriele Bonatz, Janine Altmüller, Christian Becker, Günter Gisselmann, Hanns Hatt
Transient receptor potential (TRP) channels contribute to the regulation of intracellular calcium, which can promote cancer hallmarks in cases of dysregulation of gene transcription and calcium-dependent pro-proliferative or anti-apoptotic mechanisms. Several studies have begun to elucidate the roles of TRPV1, TRPV6, TRPM8, and TRPC1 in cancer progression; however, no study has examined the expression profiles of human TRP channels in breast cancer on a large scale. This study focused on the expression and functionality of TRPV1, a nonselective cation channel that was found to be expressed in different carcinoma tissues...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28003585/cold-stimulation-evokes-exocytotic-vesicle-release-from-pc12-cells
#11
Ryoichi Yoshimura, Misaki Nakagawa, Yasuhisa Endo
The mechanism of peripheral blood circulation failure by low temperatures, known as Raynaud's phenomenon, is not well understood at present. We examined the possibility that the efferent fibers of peripheral sympathetic neurons may release transmitters directly by cold sensation. PC12 cells, a culture model of sympathetic neurons, were placed at 25°C for 30 min, fixed with the tannic acid-glutaraldehyde-osmium method and observed by electron microscopy. The number of omega-shaped exocytotic vesicle figures increased significantly compared with that in the control (37°C), although it was lower than that of the positive control (high potassium stimulation at 25°C and 37°C)...
2016: Biomedical Research
https://www.readbyqxmd.com/read/27964995/synthesis-and-optimization-of-novel-%C3%AE-phenylglycinamides-as-selective-trpm8-antagonists
#12
Jun-Ichi Kobayashi, Hideaki Hirasawa, Tetsuji Ozawa, Tomonaga Ozawa, Hiroo Takeda, Yoshikazu Fujimori, Osamu Nakanishi, Noboru Kamada, Tetsuya Ikeda
Transient receptor potential melastatin 8 (TRPM8) is activated by innocuous cold and chemical substances, and antagonists of this channel have been considered to be effective for pain and urinary diseases. N-(3-aminopropyl)-2-{[(3-methylphenyl)methyl]oxy}-N-(2-thienylmethyl)benzamide hydrochloride (AMTB), a TRPM8 antagonist, was proposed to be effective for overactive bladder and painful bladder syndrome; however, there is a potential risk of low blood pressure. We report herein the synthesis and structure-activity relationships of novel phenylglycine derivatives that led to the identification of KPR-2579 (20l), a TRPM8 selective antagonist...
January 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27875791/localization-and-expression-patterns-of-trp-channels-in-submandibular-gland-development
#13
Motoya Fujiseki, Masahito Yamamoto, Sobhan Ubaidus, Takashi Shinomiya, Shinichi Abe, Masakazu Tazaki, Hitoshi Yamamoto
OBJECTIVE: Expression of Transient receptor potential (TRP) channels: TRP canonical (TRPC)1, TRP vanilloid (TRPV)3, TRPV4 and TRP melastatin (TRPM)8 in adult rat salivary gland has recently been reported. The authors investigated expression of these TRP channels in the submandibular gland during early developmental stage in which the cell constitution is different, and discussed the function of TRP in the submandibular gland in early development. DESIGN: Using rat submandibular gland at embryonic days (E)18 and E20 and postnatal days (PN)0 and PN5 and PN28, expression of TRPV3, TRPV4, TRPC1 and TRPM8 was investigated using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry...
February 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/27864675/drugs-affecting-trp-channels
#14
M A Wortley, M A Birrell, M G Belvisi
Chronic obstructive pulmonary disease (COPD) and asthma are both common respiratory diseases that are associated with airflow reduction/obstruction and pulmonary inflammation. Whilst drug therapies offer adequate symptom control for many mild to moderate asthmatic patients, severe asthmatics and COPD patients symptoms are often not controlled, and in these cases, irreversible structural damage occurs with disease progression over time. Transient receptor potential (TRP) channels, in particular TRPV1, TRPA1, TRPV4 and TRPM8, have been implicated with roles in the regulation of inflammation and autonomic nervous control of the lungs...
November 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27862339/novel-trpm8-agonist-cooling-compound-against-chronic-itch-results-from-a-randomized-double-blind-controlled-pilot-study-in-dry-skin
#15
S Ständer, M Augustin, D Roggenkamp, C Blome, T Heitkemper, A C Worthmann, G Neufang
BACKGROUND: Patients suffering from chronic pruritus (CP) due to dry skin with are often applying emollients containing menthol. However, topical menthol may be irritating and of weak potency in severe pruritus. Two TRPM8 agonists, (1R,2S,5R)-N-(2-(2-pyridinyl)ethyl)-2-ispropyl-5-methylcyclohexancarboxamide and menthoxypropanediol, combined as cooling compound (CC) have shown stronger activation of TRPM8 than menthol. OBJECTIVES: Objective of this study was to evaluate the efficacy and safety of CC in alleviating pruritus in patients with dry itchy skin...
November 11, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27845197/sustained-morphine-administration-induces-trpm8-dependent-cold-hyperalgesia
#16
Kerui Gong, Luc Jasmin
: It is not uncommon for patients chronically treated with opioids to exhibit opioid-induced hyperalgesia, and this has been widely reported clinically and experimentally. The molecular substrate for this hyperalgesia is multifaceted, and associated with a complex neural reorganization even in the periphery. For instance, we have recently shown that chronic morphine-induced heat hyperalgesia is associated with an increased expression of GluN2B containing N-methyl-D-aspartate receptors, as well as of the neuronal excitatory amino acid transporter 3/excitatory amino acid carrier 1, in small-diameter primary sensory neurons only...
February 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/27835802/transient-receptor-potential-channels-in-neuropathic-pain
#17
REVIEW
Lilian Basso, Christophe Altier
Neuropathic pain caused by disease or dysfunction of the nervous system is one of the most difficult pain conditions to treat. Symptoms include a hypersensitivity to mechanical and thermal stimuli, processed by specialized nociceptors that constitute the first line of defence of the somatosensory system. The detection of these stimuli depends on the TRP ion channel family, which activates upon damaging pressure, extreme temperature, or toxic endogenous and exogenous chemicals. This review will summarize the current knowledge of the contribution of TRP channels, particularly the thermosensitive TRP, including TRPV1, TRPA1 and TRPM8 channels that play a central role in the sensitization of nociceptive transduction...
October 27, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27812120/oxidized-phospholipid-oxpapc-activates-trpa1-and-contributes-to-chronic-inflammatory-pain-in-mice
#18
Boyi Liu, Yan Tai, Ana I Caceres, Satyanarayana Achanta, Shrilatha Balakrishna, Xiaomei Shao, Junfan Fang, Sven-Eric Jordt
Oxidation products of the naturally occurring phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), which are known as OxPAPC, accumulate in atherosclerotic lesions and at other sites of inflammation in conditions such as septic inflammation and acute lung injury to exert pro- or anti-inflammatory effects. It is currently unknown whether OxPAPC also contributes to inflammatory pain and peripheral neuronal excitability in these conditions. Here, we observed that OxPAPC dose-dependently and selectively activated human TRPA1 nociceptive ion channels expressed in HEK293 cells in vitro, without any effect on other TRP channels, including TRPV1, TRPV4 and TRPM8...
2016: PloS One
https://www.readbyqxmd.com/read/27792844/hydrogen-peroxide-preferentially-activates-capsaicin-sensitive-high-threshold-afferents-via-trpa1-channels-in-the-guinea-pig-bladder
#19
S Nicholas, S Y Yuan, S J H Brookes, N J Spencer, V P Zagorodnyuk
BACKGROUND AND PURPOSE: There is increasing evidence suggesting that ROS play a major pathological role in bladder dysfunction induced by bladder inflammation and/or obstruction. The aim of this study was to determine the effect of H2 O2 on different types of bladder afferents and its mechanism of action on sensory neurons in the guinea pig bladder. EXPERIMENTAL APPROACH: 'Close-to-target' single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder, in flat sheet preparations, in vitro...
January 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27789940/trpm8-genetic-variations-associated-with-copd-risk-in-the-chinese-han-population
#20
Mingmei Xiong, Jian Wang, Meihua Guo, Qipeng Zhou, Wenju Lu
TRPM8 plays a key role in COPD. The development of pulmonary hypertension (PH) in COPD adversely affects survival and exercise capacity. Thus, the aim of this study was to evaluate the possible association between single nucleotide polymorphisms (SNPs) in TRPM8 and COPD or PH in COPD among the Chinese Han population. A total of 513 COPD patients and 506 controls were enrolled in the study. Six tag SNPs (tSNPs) were genotyped. The relationship between COPD or PH in COPD and the six tSNPs was evaluated using the χ(2) test and genetic model analysis...
2016: International Journal of Chronic Obstructive Pulmonary Disease
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