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https://www.readbyqxmd.com/read/28440188/trp-channels-as-novel-targets-for-endogenous-ligands-focus-on-endocannabinoids-and-nociceptive-signalling
#1
Maksim V Storozhuk, Alexander V Zholos
The endocannabinoid system is gaining steadily increasing research interest as its important role in the regulation of many fundamental physiological processes becomes more and more evident. One area which received particularly significant attention concerns targeting the endocannabinoid system as a useful strategy in pain control, especially in refractory, difficult to treat cases of chronic pain. Apart from the classical targets of cannabinoids, the CB1 and CB2 receptors, several members of the large TRP family of Ca2+-permeable cation channels have been designated as "ionotropic cannabinoid receptors" to highlight their role in cannabinoid signalling...
April 24, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28439004/endocannabinoid-system-acts-as-a-regulator-of-immune-homeostasis-in-the-gut
#2
Nandini Acharya, Sasi Penukonda, Tatiana Shcheglova, Adam T Hagymasi, Sreyashi Basu, Pramod K Srivastava
Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438966/mediation-of-movement-induced-breakthrough-cancer-pain-by-ib4-binding-nociceptors-in-rats
#3
Joshua Havelin, Ian Imbert, Devki Sukhtankar, Bethany Remeniuk, Ian Pelletier, Jonathan Gentry, Alec Okun, Timothy Tiutan, Frank Porreca, Tamara King
Cancer-induced bone pain (CIBP) is characterized by moderate to severe ongoing pain that commonly requires the use of opiates. Even when ongoing pain is well controlled, patients can suffer breakthrough pain (BTP), episodic severe pain that "breaks through" the medication. We developed a novel model of cancer-induced BTP using female rats with mammary adenocarcinoma cells sealed within the tibia. We previously demonstrated that rats with bone cancer learn to prefer a context paired with saphenous nerve block to elicit pain relief (i...
April 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28434588/the-endocannabinoid-system-as-a-target-for-novel-anxiolytic-drugs
#4
REVIEW
Sachin Patel, Mathew N Hill, Joseph F Cheer, Carsten T Wotjak, Andrew Holmes
The endocannabinoid (eCB) system has attracted attention for its role in various behavioral and brain functions, and as a therapeutic target in neuropsychiatric disease states, including anxiety disorders and other conditions resulting from dysfunctional responses to stress. In this mini-review, we highlight components of the eCB system that offer potential 'druggable' targets for new anxiolytic medications, emphasizing some of the less well-discussed options. We discuss how selectively amplifying eCBs recruitment by interfering with eCB-degradation, via fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), has been linked to reductions in anxiety-like behaviors in rodents and variation in human anxiety symptoms...
May 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28433438/analgesic-effects-of-transcutaneous-ultrasound-nerve-stimulation-in-a-rat-model-of-oxaliplatin-induced-mechanical-hyperalgesia-and-cold-allodynia
#5
Yueh-Ling Hsieh, Han-Yu Chen, Ching-Hsiang Yang, Chen-Chia Yang
This study investigated the effects and underlying mechanisms of therapeutic ultrasound (TUS) in a rat model of oxaliplatin-induced peripheral neuropathy. Animals received a total of eight injections with oxaliplatin (4 mg/kg), administered at 3-d intervals. TUS intervention (1 MHz, 0.5 W/cm(2)) started on the fifth oxaliplatin administration and continued for 10 consecutive d. Sensory behavioral examinations, protein levels of transient receptor potential channels (TRPM8 and TRPV1) in dorsal root ganglia (DRG) and substance P (SP) in spinal dorsal horn were examined...
April 19, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28432255/osmotic-activation-of-a-ca-2-dependent-phospholipase-c-pathway-that-regulates-%C3%A2-n-trpv1-mediated-currents-in-rat-supraoptic-neurons
#6
Vimal Bansal, Thomas E Fisher
The magnocellular neurosecretory cells (MNCs) of the hypothalamus regulate body fluid balance by releasing the hormones vasopressin (VP) and oxytocin (OT) in an osmolality-dependent manner. Elevations of external osmolality increase MNC firing and hormone release. MNC osmosensitivity is largely due to activation of a mechanosensitive non-selective cation current that responds to osmotically-evoked changes in MNC volume and is mediated by an N-terminal variant of the TRPV1 channel (∆N TRPV1). We report a novel mechanism by which increases in osmolality may modulate ∆N TRPV1-mediated currents and thus influence MNC electrical behaviour...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28422079/synthetic-fluororutaecarpine-inhibits-inflammatory-stimuli-and-activates-endothelial-transient-receptor-potential-vanilloid-type-1
#7
Chi-Ming Lee, Jiun-An Gu, Tin-Gan Rau, Chi Wang, Chiao-Han Yen, Shih-Hao Huang, Feng-Yen Lin, Chun-Mao Lin, Sheng-Tung Huang
The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that showed no cytotoxicity toward RAW264.7 macrophages at 20 μM. In an anti-inflammation experiment, it inhibited the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW264...
April 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28418433/capsaicin-presynaptically-inhibits-glutamate-release-through-the-activation-of-trpv1-and-calcineurin-in-the-hippocampus-of-rats
#8
Cheng Wei Lu, Tzu Yu Lin, Ting Yang Hsie, Shu Kuei Huang, Su Jane Wang
Capsaicin is the major ingredient in hot peppers of the plant Capsicum genus with neuroprotective effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus using isolated nerve terminals (synaptosomes) and brain slices. In a synaptosomal preparation, capsaicin dose-dependently reduced 4-aminopyridine-evoked Ca(2+)-dependent glutamate release, with an IC50 of approximately 11 μM. This inhibition was blocked by capsazepin, an antagonist of TRPV1, which was found to be colocalized with the vesicle marker protein synaptophysin in synaptosomes using double immunostaining...
April 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28416203/the-s4-s5-linker-gearbox-of-trp-channel-gating
#9
REVIEW
Laura Hofmann, Hongmei Wang, Wang Zheng, Stephan E Philipp, Patricia Hidalgo, Adolfo Cavalié, Xing-Zhen Chen, Andreas Beck, Veit Flockerzi
Transient receptor potential (TRP) channels are cation channels which participate in a wide variety of physiological processes in organisms ranging from fungi to humans. They fulfill roles in body homeostasis, are sensors for noxious chemicals and temperature in the mammalian somatosensory system and are activated by light stimulated phospholipase C activity in Drosophila or by hypertonicity in yeast. The transmembrane topology of TRP channels is similar to that of voltage-gated cation channels. TRP proteins assemble as tetramers with each subunit containing six transmembrane helices (S1-S6) and intracellular N- and C-termini...
April 4, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28413758/de-novo-modular-development-of-a-foldameric-protein-protein-interaction-inhibitor-for-separate-hot-spots-a-dynamic-covalent-assembly-approach
#10
Éva Bartus, Zsófia Hegedüs, Edit Wéber, Brigitta Csipak, Gerda Szakonyi, Tamás A Martinek
Protein-protein interactions stabilized by multiple separate hot spots are highly challenging targets for synthetic scaffolds. Surface-mimetic foldamers bearing multiple recognition segments are promising candidate inhibitors. In this work, a modular bottom-up approach is implemented by identifying short foldameric recognition segments that interact with the independent hot spots, and connecting them through dynamic covalent library (DCL) optimization. The independent hot spots of a model target (calmodulin) are mapped with hexameric β-peptide helices using a pull-down assay...
April 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28410966/vincristine-induced-peripheral-neuropathic-pain-and-expression-of-transient-receptor-potential-vanilloid-1-in-rat
#11
Terumasa Chiba, Yusuke Oka, Hiroya Sashida, Toshie Kanbe, Kenji Abe, Iku Utsunomiya, Kyoji Taguchi
The clinical anti-cancer efficacy of vincristine is limited by the development of dose-dependent peripheral neuropathy. Up-regulation of transient receptor potential vanilloid 1 (TRPV1) is correlated with peripheral neuropathy following anti-cancer drug treatment. To analyze the contribution of TRPV1 to the development of vincristine-induced mechanical allodynia/hyperalgesia, TRPV1 expression in the rat dorsal root ganglion (DRG) was analyzed after vincristine treatment. Mechanical allodynia/hyperalgesia was tested with von Frey filaments 14 days after intraperitoneal administration of 0...
March 30, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28410268/long-term-anti-itch-effect-of-botulinum-neurotoxin-a-is-associated-with-downregulation-of-trpv1-and-trpa1-in-the-dorsal-root-ganglia-in-mice
#12
Lei-Fang Cao, Meng Si, Ya Huang, Li-Hua Chen, Xiao-Yan Peng, Ya-Qin Qin, Teng-Teng Liu, Yan Zhou, Tong Liu, Wei-Feng Luo
Itch is a common symptom in patients with skin and systemic diseases, but the effective treatment is limited. Here, we evaluated the anti-itch effects of the botulinum toxin type A (BoNT/A) using acute and chronic dry skin itch mouse models, which were induced by compound 48/80, chloroquine, and a mixture of acetone-diethylether-water treatment, respectively. Pretreatment of intradermal BoNT/A exerted long-term inhibitory effects on compound 48/80-induced and chloroquine-induced acute itch on days 1, 3, 7, and 14, but not on day 21, in mice...
April 13, 2017: Neuroreport
https://www.readbyqxmd.com/read/28404507/paclitaxel-inhibits-the-activity-and-membrane-localization-of-pkc%C3%AE-and-pkc%C3%AE-i-ii-to-elicit-a-decrease-in-stimulated-calcitonin-gene-related-peptide-release-from-cultured-sensory-neurons
#13
Lisa M Darby, Hongdi Meng, Jill C Fehrenbacher
Peripheral neuropathy is a dose-limiting and debilitating side effect of the chemotherapeutic drug, paclitaxel. Consequently, elucidating the mechanisms by which this drug alters sensory neuronal function is essential for the development of successful therapeutics for peripheral neuropathy. We previously demonstrated that chronic treatment with paclitaxel (3-5days) reduces neuropeptide release stimulated by agonists of TRPV1. Because the activity of TRPV1 channels is modulated by conventional and novel PKC isozymes (c/nPKC), we investigated whether c/nPKC mediate the loss of neuropeptide release following chronic treatment with paclitaxel (300nM; 3 and 5days)...
April 9, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28402861/trpv1-regulates-stress-responses-through-hdac2
#14
Sung Eun Wang, Seung Yeon Ko, Sungsin Jo, Miyeon Choi, Seung Hoon Lee, Hye-Ryeong Jo, Jee Young Seo, Sang Hoon Lee, Yong-Seok Kim, Sung Jun Jung, Hyeon Son
Stress causes changes in neurotransmission in the brain, thereby influencing stress-induced behaviors. However, it is unclear how neurotransmission systems orchestrate stress responses at the molecular and cellular levels. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel involved mainly in pain sensation, affects mood and neuroplasticity in the brain, where its role is poorly understood. Here, we show that Trpv1-deficient (Trpv1(-/-)) mice are more stress resilient than control mice after chronic unpredictable stress...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28400256/n-oleoyldopamine-modulates-activity-of-midbrain-dopaminergic-neurons-through-multiple-mechanisms
#15
Olga A Sergeeva, Roberto De Luca, Karolina Mazur, Aissa N Chepkova, Helmut L Haas, Andreas Bauer
N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic neurons. The present study investigates OLDA targets in midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons recorded in brain slices were excited by OLDA in wild type mice. In transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA neurons displayed sustained inhibition of firing. In the presence of the dopamine type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker nomifensine no such inhibition was observed...
April 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28398734/construction-of-prediction-models-for-the-transient-receptor-potential-vanilloid-subtype-1-trpv1-stimulating-activity-of-ginger-and-processed-ginger-based-on-lc-hrms-data-and-pls-regression-analyses
#16
Taichi Yoshitomi, Naohiro Oshima, Yuto Goto, Shunsuke Nakamori, Daigo Wakana, Naoko Anjiki, Koji Sugimura, Noriaki Kawano, Hiroyuki Fuchino, Osamu Iida, Toshiko Kagawa, Hideto Jinno, Nobuo Kawahara, Yoshinori Kobayashi, Takuro Maruyama
To construct a model formula to evaluate the thermogenetic effect of ginger (Zingiber officinale Roscoe) from the ingredient information, we established transient receptor potential vanilloid subtype 1 (TRPV1)-stimulating activity prediction models by using a partial least-squares projections to latent structures (PLS) regression analysis in which the ingredient data from liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and the stimulating activity values for TRPV1 receptor were used as explanatory and objective variables, respectively...
April 19, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28391533/the-validation-of-calophyllum-brasiliense-guanandi-uses-in-brazilian-traditional-medicine-as-analgesic-by-in-vivo-antinociceptive-evaluation-and-its-chemical-analysis
#17
Luiz Carlos Klein-Júnior, Daniele Zambiasi, Giovana Rocha Salgado, Franco Delle Monache, Valdir Cechinel Filho, Fátima de Campos Buzzi
Calophyllum brasiliense is used as anti-inflammatory and analgesic in Brazilian traditional medicine. Thus, the main purpose of this study is to evaluate the antinociceptive effect of the chloroform fraction of C. brasiliense (CFCB) roots and to investigate its main mechanism of action. The antinociceptive effect of CFCB was evaluated in mice using acetic acid-induced writhing, formalin-induced paw licking, and hot-plate tests and capsaicin- and glutamate-induced nociception. Brasiliensic acid and 1,2-dimethoxyxanthone were isolated and evaluated in writhing test...
April 8, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28386183/establishment-of-preliminary-regulatory-network-of-trpv1-and-related-cytokines
#18
Jianhua Zhang, Zheng Zhou, Ning Zhang, Wenwen Jin, Yafeng Ren, Chuanliang Chen
Our purpose was to investigate the regulatory mechanism of TRPV1 and related cytokines on children bronchial asthma. TRPV1 mRNA level and two SNP genotypes of children in case group and control group were detected by real-time quantitative PCR. Western blot and ELISA were used to measure the levels of cytokines like IgE, IL-2, etc. Their correlations were analyzed by Logistic regression and KEGG analysis. Moreover, tertiary structure of protein and miRNA binding sites were also predicted by online tools. Case group was obviously different from control group in TRPV1 mRNA level, the two SNP genotypes distribution and the related cytokines levels...
March 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28385695/transient-receptor-potential-ion-channel-function-in-sensory-transduction-and-cellular-signaling-cascades-underlying-visceral-hypersensitivity
#19
Dafne Balemans, Guy E Boeckxstaens, Karel Talavera, Mira M Wouters
Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28385191/stz-causes-depletion-of-immune-cells-in-sciatic-nerve-and-dorsal-root-ganglion-in-experimental-diabetes
#20
Asa S Hidmark, Peter P Nawroth, Thomas Fleming
Streptozotocin (STZ) treatment, a common model for inducing diabetes in rodent models, induces thermal hyperalgesia and neuronal toxicity independently of hyperglycemia by oxidizing and activating TRPA1 and TRPV1. Following treatment with STZ, CD45(+) immune cells were found to be depleted in sciatic nerve (SN) and DRG in mice, prior to hyperglycemia. Macrophages were also lost in DRG and NFκB-p65-activation was increased in SN macrophages. Immune cells were significantly reduced in both SN and DRG up to three weeks, post-treatment...
May 15, 2017: Journal of Neuroimmunology
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