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https://www.readbyqxmd.com/read/28640864/targeting-breast-cancer-cells-by-mrs1477-a-positive-allosteric-modulator-of-trpv1-channels
#1
Mustafa Nazıroğlu, Bilal Çiğ, Walter Blum, Csaba Vizler, Andrea Buhala, Annamária Marton, Róbert Katona, Katalin Jósvay, Beat Schwaller, Zoltán Oláh, László Pecze
There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28635651/effects-of-tetrodotoxin-in-mouse-models-of-visceral-pain
#2
Rafael González-Cano, Miguel Ángel Tejada, Antonia Artacho-Cordón, Francisco Rafael Nieto, José Manuel Entrena, John N Wood, Cruz Miguel Cendán
Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28631948/possible-contribution-of-pannexin-1-to-capsaicin-induced-atp-release-in-rat-nasal-columnar-epithelial-cells
#3
Toyoaki Ohbuchi, Ba Hung Do, Hiroki Koizumi, Shoko Takeuchi, Yoichi Ueta, Hideaki Suzuki
Current evidence indicates that transient receptor potential (TRP) channel activity involves a relationship between opening of pannexin-1 and release of ATP into the extracellular space. We examined the effects of agonists of thermosensitive TRP channels (TRPM8, TRPA1, TRPV1, and TRPV2) on ATP release from rat nasal mucosa, and measured ciliary beat frequency (CBF) using digital high-speed video imaging. Single-cell patch clamping from dissociated rat nasal columnar epithelial cells was performed to confirm the relationship between pannexin-1 and TRP...
February 10, 2017: Channels
https://www.readbyqxmd.com/read/28629730/synergistic-antinociceptive-effect-of-a-calcium-channel-blocker-and-a-trpv1-blocker-in-an-acute-pain-model-in-mice
#4
Manuella R Palhares, Juliana F Silva, Marcio Junior S Rezende, Duana C Santos, Cláudio A Silva-Junior, Márcia H Borges, Juliano Ferreira, Marcus V Gomez, Célio J Castro Junior
AIMS: Extensive evidence supports a role for voltage-gated calcium channels (VGCC) and TRPV1 receptors in pain transmission and modulation. We investigated the profile of analgesic interaction between Phα1β toxin (a VGCC blocker) and SB366791 (selective TRPV1 antagonist) in a model of acute pain induced by capsaicin. Changes in body temperature induced by combination regimens were also evaluated. MAIN METHODS: Isobolographic approach with a fixed dose-ratio of combined drugs was used to determine whether antinociceptive interaction of Phα1β and SB366791 are subadditive, additive or synergic...
June 16, 2017: Life Sciences
https://www.readbyqxmd.com/read/28627264/utility-of-in-vitro-and-in-vivo-systems-for-studying-the-permeability-of-capsaicin-and-nonivamide-through-different-intestinal-regions
#5
Lian Duan, Huaidong Peng, Guangcan Li, Ruolun Wang, Yanfang Chen
1. The present study determined and compared the permeability of capsaicin and nonivamide along the length of the intestine in rats. Accordingly, to evaluate this synthetic analog as a clinical substitute for capsaicin. 2. Permeabilities of capsaicin and nonivamide were measured in experiments utilizing Ussing chambers and in vivo methods. Capsaicin concentrations were examined by Liquid chromatography tandem mass spectrometry (LC-MS/MS). 3. Both capsaicin (0.80 × 10(-6) cm/s) and nonivamide (0.22 × 10(-6) cm/s, P > 0...
June 19, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28622417/the-antimigraine-butterbur-ingredient-isopetasin-desensitises-peptidergic-nociceptors-via-the-transient-receptor-potential-ankyrin-1-channel
#6
Silvia Benemei, Francesco De Logu, Simone Li Puma, Ilaria Maddalena Marone, Elisabetta Coppi, Filippo Ugolini, Wolfgang Liedtke, Pollastro Federica, Giovanni Appendino, Pierangelo Geppetti, Serena Materazzi, Romina Nassini
BACKGROUND AND PURPOSE: The mechanism of the antimigraine action of butterbur [Petasites hybridus (L.) Gaertn.] is unknown. Here, we investigated the ability of isopetasin, a major butterbur constituent, to specifically target the transient receptor ankyrin 1 (TRPA1) channel and to affect functional responses relevant to migraine. EXPERIMENTAL APPROACH: Single cell calcium imaging and patch-clamp recordings in human and rodent TRPA1-expressing cells, neurogenic motor responses in isolated rat/mouse urinary bladder, release of calcitonin gene-related peptide (CGRP) from mouse spinal cord in vitro, and facial rubbing in mice and meningeal blood flow in rat were examined...
June 16, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28620309/inhibition-of-the-trpm2-and-trpv1-channels-through-hypericum-perforatum-in-sciatic-nerve-injury-induced-rats-demonstrates-their-key-role-in-apoptosis-and-mitochondrial-oxidative-stress-of-sciatic-nerve-and-dorsal-root-ganglion
#7
Fuat Uslusoy, Mustafa Nazıroğlu, Bilal Çiğ
Sciatic nerve injury (SNI) results in neuropathic pain, which is characterized by the excessive Ca(2+) entry, reactive oxygen species (ROS) and apoptosis processes although involvement of antioxidant Hypericum perforatum (HP) through TRPM2 and TRPV1 activation has not been clarified on the processes in SNI-induced rat, yet. We investigated the protective property of HP on the processes in the sciatic nerve and dorsal root ganglion neuron (DRGN) of SNI-induced rats. The rats were divided into five groups as control, sham, sham+HP, SNI, and SNI+HP...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28618110/intravesical-vanilloids-for-treating-neurogenic-lower-urinary-tract-dysfunction-in-patients-with-multiple-sclerosis-a-systematic-review-and-meta-analysis-a-report-from-the-neuro-urology-promotion-committee-of-the-international-continence-society-ics
#8
REVIEW
Véronique Phé, Marc P Schneider, Benoit Peyronnet, Nadim Abo Youssef, Livio Mordasini, Emmanuel Chartier-Kastler, Lucas M Bachmann, Thomas M Kessler
AIMS: To systematically assess all available evidence on efficacy and safety of vanilloids for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS). METHODS: This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Cochrane register, Embase, Medline, Scopus, (last search January 8, 2016)...
June 15, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28615326/prenatal-nicotinic-exposure-prolongs-superior-laryngeal-c-fiber-mediated-apnea-and-bradycardia-through-enhancing-neuronal-trpv1-expression-and-excitation
#9
Xiuping Gao, Lei Zhao, Jianguo Zhuang, Na Zang, Fadi Xu
Maternal cigarette smoke, including prenatal nicotinic exposure (PNE), is responsible for sudden infant death syndrome (SIDS). The fatal events of SIDS are characterized by severe bradycardia and life-threatening apneas. Although activation of transient receptor potential vanilloid 1 (TRPV1) of superior laryngeal C-fibers (SLCFs) could induce bradycardia and apnea and has been implicated in SIDS pathogenesis, how PNE affects the SLCF-mediated cardiorespiratory responses remains unexplored. Here, we tested the hypothesis that PNE would aggravate the SLCF-mediated apnea and bradycardia via up-regulating TRPV1 expression and excitation of laryngeal C-neurons in the nodose/jugular (N/J) ganglia...
June 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28606782/role-of-peripheral-and-central-trpv1-receptors-in-facial-heat-hyperalgesia-in-streptozotocin-induced-diabetic-rats
#10
Erika IvannaAraya, Carina Fernanda MattediNones, Luiz Eduardo Nunes Ferreira, Caroline Machado Kopruszinski, Joice Maria da Cunha, Juliana GeremiasChichorro
There is increasing evidence that diabetes may be related to sensory changes in the trigeminal system. Long lasting facial heat hyperalgesia has been described in diabetic rats, but the mechanisms remain to be elucidated. Herein, the contribution of peripheral and central TRPV1 receptors to facial heat hyperalgesia in diabeticrats was investigated. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.p) and facial heat hyperalgesia was assessed once a week up to four weeks. The role of TRPV1 receptors in the heat hyperalgesia in diabetic rats was evaluated through: 1) the ablation of TRPV1 receptors by resiniferatoxin (RTX) treatment and 2) injection of the TRPV1 antagonist,capsazepine, into the upper lip, trigeminal ganglion or medullary subarachnoid space, at doses that completed prevented the heat hyperalgesia induced by capsaicin in naïve rats...
June 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28602628/overexpression-of-fibulin-5-attenuates-burn-induced-inflammation-via-trpv1-cgrp-pathway
#11
Xiaoqian Hou, Hui Li, Chunhua Zhang, Junling Wang, Xiuli Li, Xin Li
Fibulin-5, a multifunctional extracellular matrix protein, is up-regulated in response to mechanical injury and can promote dermal wound healing. This study aimed to explore the role and mechanism of Fibulin-5 in the pathogenesis of post-burn inflammation in thermally-injured mice. Here, we found that Fibulin-5 was up-regulated in the dorsal root ganglion (DRG) of burn-injured mice. After nociceptive behavioral testing, DRG was isolated and cultured to detect the mechanism of Fibulin-5 in thermal injury models by recombinant adenovirus overexpressing Fibulin-5, RT-qPCR, Western Blot, ELISA, AP20187 (an activator of one kind of kinase phosphorylating the α subunit of eukaryotic initiation factor 2, eIF2α), capsaicin (an agonist of transient receptor potential vanilloid (TRPV)-1), and an anti-CGRP neutralizing antibody...
June 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28599085/exploring-the-putative-role-of-trpv1-dependent-cgrp-release-in-remote-hind-preconditioning-induced-cardioprotection
#12
Puneet Kaur Randhawa, Amteshwar Singh Jaggi
Remote ischemic preconditioning (RIPC) is a phenomenon whereby transient non-lethal ischemia and reperfusion episodes confer protection against prolonged ischemia-reperfusion-induced injury. However, the underlying intracellular signaling has not been extensively explored. The present study aims to inspect the putative involvement of TRPV1 -dependent CGRP release in mediating remote hind limb preconditioning-induced cardioprotection. In the present study, remote hind limb preconditioning stimulus was delivered (4 consecutive episodes of 5 minutes of ischemia-reperfusion) using a blood pressure cuff tied at the inguinal level of the rat...
June 9, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28598691/development-of-68-ga-scn-dota-capsaicin-as-an-imaging-agent-targeting-apoptosis-and-cell-cycle-arrest-in-breast-cancer
#13
Jun Young Lee, Sang-Yeun Lee, Gun Gyun Kim, Min Goo Hur, Seung Dae Yang, Jeong-Hoon Park, Sang Wook Kim
(68)Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [(68)Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, (69)Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of (68)Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes)...
June 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28595182/the-effect-of-dietary-supplements-containing-green-tea-capsaicin-and-ginger-extracts-on-weight-loss-and-metabolic-profiles-in-overweight-women-a-randomized-double-blind-placebo-controlled-clinical-trial
#14
Mohsen Taghizadeh, Narjes Farzin, Sara Taheri, Mahnaz Mahlouji, Hossein Akbari, Fatemeh Karamali, Zatollah Asemi
BACKGROUND: This study was conducted to determine the effects of dietary supplements containing green tea, capsaicin and ginger extracts on weight loss and metabolic profiles among overweight women. METHODS: This randomized double-blind placebo-controlled clinical trial was implemented among 50 overweight women. Participants were randomly divided into 2 groups. Group A received dietary supplements containing 125 mg green tea, 25 mg capsaicin and 50 mg ginger extracts (n = 25) group B received placebos (n = 25) twice with lunch and twice with dinner daily for 8 weeks...
June 9, 2017: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/28593473/pharmacokinetic-pharmacodynamic-relationship-of-erenumab-amg-334-and-capsaicin-induced-dermal-blood-flow-in-healthy-and-migraine-subjects
#15
Thuy Vu, Peiming Ma, Jiyun Sunny Chen, Jan de Hoon, Anne Van Hecken, Lucy Yan, Liviawati Sutjandra Wu, Lisa Hamilton, Gabriel Vargas
PURPOSE: Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy and migraine subjects. METHODS: Repeated capsaicin challenges and DBF measurements were performed and serum erenumab concentrations determined...
June 7, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28587873/regulation-of-transient-receptor-potential-cation-channel-subfamily-v1-protein-synthesis-by-the-phosphoinositide-3-kinase-akt-pathway-in-colonic-hypersensitivity
#16
Shanwei Shen, Hamad W Al-Thumairy, Fiza Hashmi, Li-Ya Qiao
The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor or vanilloid receptor 1 (VR1), is expressed in nociceptive neurons in the dorsal root ganglia (DRG) and participates in the transmission of pain. The present study investigated the underlying molecular mechanisms by which TRPV1 was regulated by nerve growth factor (NGF) signaling pathways in colonic hypersensitivity in response to colitis. We found that during colitis TRPV1 protein levels were significantly increased in specifically labeled colonic afferent neurons in both L1 and S1 DRGs...
June 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28587842/sustained-sensitizing-effects-of-tumor-necrosis-factor-alpha-on-sensory-nerves-in-lung-and-airways
#17
REVIEW
Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee
Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 h later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and cytokines in the lung and airways...
June 3, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28587509/-express-differential-involvement-of-reactive-oxygen-species-in-a-mouse-model-of-capsaicin-induced-secondary-mechanical-hyperalgesia-and-allodynia
#18
Jun-Ho La, Jigong Wang, Alice Bittar, Hyun Soo Shim, Chilman Bae, Jin Mo Chung
No abstract text is available yet for this article.
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28587440/comparative-metabolomics-in-vanilla-pod-and-vanilla-bean-revealing-the-biosynthesis-of-vanillin-during-the-curing-process-of-vanilla
#19
Fenglin Gu, Yonggan Chen, Yinghua Hong, Yiming Fang, Lehe Tan
High-performance liquid chromatography-mass spectrometry (LC-MS) was used for comprehensive metabolomic fingerprinting of vanilla fruits prepared from the curing process. In this study, the metabolic changes of vanilla pods and vanilla beans were characterized using MS-based metabolomics to elucidate the biosynthesis of vanillin. The vanilla pods were significantly different from vanilla beans. Seven pathways of vanillin biosynthesis were constructed, namely, glucovanillin, glucose, cresol, capsaicin, vanillyl alcohol, tyrosine, and phenylalanine pathways...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28579775/capsaicin-loaded-nanolipoidal-carriers-for-topical-application-design-characterization-and-in-vitro-in-vivo-evaluation
#20
Xia-Rong Wang, Si-Qian Gao, Xiao-Qian Niu, Long-Jian Li, Xiao-Ying Ying, Zhong-Jie Hu, Jian-Qing Gao
Capsaicin has been used in clinical applications for the treatment of pain disorders and inflammatory diseases. Given the strong pungency and high oil/water partition coefficient of capsaicin, capsaicin-loaded nanolipoidal carriers (NLCs) were designed to increase permeation and achieve the analgesic, anti-inflammatory effect with lower skin irritation. Capsaicin-loaded NLCs were prepared and later optimized by the Box-Behnken design. The physicochemical characterizations, morphology, and encapsulation of the capsaicin-loaded NLCs were subsequently confirmed...
2017: International Journal of Nanomedicine
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