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https://www.readbyqxmd.com/read/28933582/dynamic-sensitivity-of-corneal-trpm8-receptors-to-menthol-instillation-in-dry-eye-versus-normal-subjects
#1
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...
September 21, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28928655/effects-of-simvastatin-beyond-dyslipidemia-exploring-its-antinociceptive-action-in-an-animal-model-of-complex-regional-pain-syndrome-type-i
#2
Graziela Vieira, Juliana Cavalli, Elaine C D Gonçalves, Tainara R Gonçalves, Larissa R Laurindo, Maíra Cola, Rafael C Dutra
Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP) was induced by ischemia and reperfusion (IR) injury of the left hind paw...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28925503/quantitative-analysis-of-mouse-dural-afferent-neurons-expressing-trpm8-vglut3-and-nf200
#3
Lynn Ren, Michelle Jaehee Chang, Zhiyu Zhang, Ajay Dhaka, Zhaohua Guo, Yu-Qing Cao
OBJECTIVE: To quantify the abundance of dural afferent neurons expressing transient receptor potential channel melastatin 8 (TRPM8), vesicular glutamate transporter 3 (VGLUT3), and neurofilament 200 (NF200) in adult mice. BACKGROUND: With the increasing use of mice as a model system to study headache mechanisms, it is important to understand the composition of dural afferent neurons in mice. In a previous study, we have measured the abundance of mouse dural afferent neurons that express neuropeptide calcitonin gene-related peptide as well as two TRP channels TRPV1 and TRPA1, respectively...
September 19, 2017: Headache
https://www.readbyqxmd.com/read/28924972/targeting-nociceptive-trp-channels-to-treat-chronic-pain-current-state-of-the-field
#4
REVIEW
Magdalene M Moran, Arpad Szallasi
Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of Transient Receptor Potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically...
September 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28923290/use-of-adult-sensory-panel-to-study-individual-differences-in-the-palatability-of-a-pediatric-hiv-treatment-drug
#5
Julie A Mennella, Phoebe S Mathew, Elizabeth D Lowenthal
PURPOSE: The recommended first-line treatment for young children infected with HIV includes the liquid formulation of the co-formulated protease inhibitors lopinavir/ritonavir (Kaletra(®) [Abbott Laboratories, Chicago, Illinois]). Clinical reports indicate that some children readily accept the taste of Kaletra, whereas others strongly reject it, which can deter therapeutic adherence and outcomes. METHODS: As a proof-of-concept approach, a sensory panel of genotyped adults was used to document the range of individual differences in the taste and palatability (hedonics) of the liquid formulation of Kaletra and other taste stimuli, including common excipients...
September 15, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28918457/effects-of-menthol-and-its-interaction-with-nicotine-conditioned-cue-on-nicotine-seeking-behavior-in-rats
#6
Erin Harrison, Lisa Biswas, Ramachandram Avusula, Meiyu Zhang, Yongzhen Gong, Xiu Liu
RATIONALE: Increasing clinical evidence suggests that menthol, a significant flavoring additive in tobacco products, may contribute to smoking and nicotine dependence. Relapse to smoking behavior presents a formidable challenge for the treatment of tobacco addiction. An unresolved issue is whether the mentholation of tobacco products precipitates relapse to tobacco use in abstinent smokers. OBJECTIVES: The present study examined the effects of menthol on the perseverance and relapse of nicotine-seeking behavior in rats...
September 16, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28903060/effects-of-curcumin-and-curcumin-analogues-on-trp-channels
#7
Marianna Nalli, Giorgio Ortar, Aniello Schiano Moriello, Vincenzo Di Marzo, Luciano De Petrocellis
A series of 33 curcumin analogues was synthesized and tested on TRPA1, TRPM8, and TRPV1 channels. Twenty of them acted as good modulators of TRPA1 channels. None was able to significantly activate TRPM8 channels, while curcumin itself and six curcuminoids belonging to the 1,3-dicarbonyl and acyclic series behaved as 'true' antagonists with IC50 values<5μM. Only few curcuminoids were able to modulate TRPV1 channels with EC50 and IC50 values ranging from 3.4 and 6.0μM.
September 10, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28887460/novel-selective-potent-naphthyl-trpm8-antagonists-identified-through-a-combined-ligand-and-structure-based-virtual-screening-approach
#8
Andrea R Beccari, Marica Gemei, Matteo Lo Monte, Nazareno Menegatti, Marco Fanton, Alessandro Pedretti, Silvia Bovolenta, Cinzia Nucci, Angela Molteni, Andrea Rossignoli, Laura Brandolini, Alessandro Taddei, Lorena Za, Chiara Liberati, Giulio Vistoli
Transient receptor potential melastatin 8 (TRPM8), a nonselective cation channel, is the predominant mammalian cold temperature thermosensor and it is activated by cold temperatures and cooling compounds, such as menthol and icilin. Because of its role in cold allodynia, cold hyperalgesia and painful syndromes TRPM8 antagonists are currently being pursued as potential therapeutic agents for the treatment of pain hypersensitivity. Recently TRPM8 has been found in subsets of bladder sensory nerve fibres, providing an opportunity to understand and treat chronic hypersensitivity...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28884838/review-article-transient-receptor-potential-channels-as-possible-therapeutic-targets-in-irritable-bowel-syndrome
#9
REVIEW
A B Beckers, Z Z R M Weerts, Z Helyes, A A M Masclee, D Keszthelyi
BACKGROUND: Abdominal pain in irritable bowel syndrome (IBS) remains challenging to treat effectively. Researchers have attempted to elucidate visceral nociceptive processes in order to guide treatment development. Transient receptor potential (TRP) channels have been implied in the generation (TRPV1, TRPV4, TRPA1) and inhibition (TRPM8) of visceral pain signals. Pathological changes in their functioning have been demonstrated in inflammatory conditions, and appear to be present in IBS as well...
September 8, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28883526/synthesis-high-throughput-screening-and-pharmacological-characterization-of-%C3%AE-lactam-derivatives-as-trpm8-antagonists
#10
Roberto de la Torre-Martínez, M Angeles Bonache, Pedro J Llabrés-Campaner, Beatriz Balsera, Asia Fernández-Carvajal, Gregorio Fernández-Ballester, Antonio Ferrer-Montiel, M Jesús Pérez de Vega, Rosario González-Muñiz
The mammalian transient receptor potential melastatin channel 8 (TRPM8), highly expressed in trigeminal and dorsal root ganglia, mediates the cooling sensation and plays an important role in the cold hypersensitivity characteristic of some types of neuropathic pain, as well as in cancer. Consequently, the identification of selective and potent ligands for TRPM8 is of great interest. Here, a series of compounds, having a β-lactam central scaffold, were prepared to explore the pharmacophore requirements for TRPM8 modulation...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28867384/downregulations-of-trpm8-expression-and-membrane-trafficking-in-dorsal-root-ganglion-mediate-the-attenuation-of-cold-hyperalgesia-in-cci-rats-induced-by-gfr%C3%AE-3-knockdown
#11
Lin Su, Ruichen Shu, Chengcheng Song, Yonghao Yu, Guolin Wang, Yazhuo Li, Changxiao Liu
BACKGROUND: Cold hyperalgesia is an intractable sensory abnormality commonly seen in peripheral neuropathies. Although glial cell line-derived neurotrophic factor family receptor alpha3 (GFRα3) is required for the formation of pathological cold pain has been revealed, potential transduction mechanism is poorly elucidated. We have previously demonstrated the contribution of enhanced activity of transient receptor potential melastatin 8 (TRPM8) to cold hyperalgesia in neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve...
September 1, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28861042/3-iodothyronamine-a-novel-endogenous-modulator-of-transient-receptor-potential-melastatin-8
#12
REVIEW
Noushafarin Khajavi, Stefan Mergler, Heike Biebermann
The decarboxylated and deiodinated thyroid hormone (TH) derivative, 3-iodothyronamine (3-T1AM), is suggested to be involved in energy metabolism and thermoregulation. G protein-coupled receptors (GPCRs) are known as the main targets for 3-T1AM; however, transient receptor potential channels (TRPs) were also recently identified as new targets of 3-T1AM. This article reviews the current knowledge of a putative novel role of 3-T1AM in the modulation of TRPs. Specifically, the TRP melastatin 8 (TRPM8) was identified as a target of 3-T1AM in different cell types including neoplastic cells, whereby 3-T1AM significantly increased cytosolic Ca(2+) through TRPM8 activation...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28857015/n-glycosylation-of-the-transient-receptor-potential-melastatin-8-channel-is-altered-in-pancreatic-cancer-cells
#13
Roxana Ulăreanu, Gabriela Chiriţoiu, Florentina Cojocaru, Alexandru Deftu, Violeta Ristoiu, Luciana Stănică, Dan F Mihăilescu, Dana Cucu
Transient receptor potential melastatin 8 (TRPM8), a membrane ion channel, is activated by thermal and chemical stimuli. In pancreatic ductal adenocarcinoma, TRPM8 is required for cell migration, proliferation, and senescence and is associated with tumor size and pancreatic ductal adenocarcinoma stages. Although the underlying mechanisms of these processes have yet to be described, this cation-permeable channel has been proposed as an oncological target. In this study, the glycosylation status of the TRPM8 channel was shown to affect cell proliferation, cell migration, and calcium uptake...
August 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#14
Irfan V Düzen, Fethi Yavuz, Ertan Vuruskan, Erhan Saracoglu, Fatih Poyraz, Hüseyin Göksülük, Basar Candemir, Seniz Demiryürek
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807145/a-benzothiadiazine-derivative-and-methylprednisolone-are-novel-and-selective-activators-of-transient-receptor-potential-canonical-5-trpc5-channels
#15
Holger Beckmann, Julia Richter, Kerstin Hill, Nicole Urban, Horst Lemoine, Michael Schaefer
The transient receptor potential canonical channel 5 (TRPC5) is a Ca(2+)-permeable ion channel, which is predominantly expressed in the brain. TRPC5-deficient mice exhibit a reduced innate fear response and impaired motor control. In addition, outgrowth of hippocampal and cerebellar neurons is retarded by TRPC5. However, pharmacological evidence of TRPC5 function on cellular or organismic levels is sparse. Thus, there is still a need for identifying novel and efficient TRPC5 channel modulators. We, therefore, screened compound libraries and identified the glucocorticoid methylprednisolone and N-[3-(adamantan-2-yloxy)propyl]-3-(6-methyl-1,1-dioxo-2H-1λ(6),2,4-benzothiadiazin-3-yl)propanamide (BTD) as novel TRPC5 activators...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28799699/a-comparative-study-on-the-therapeutic-effect-of-trpv1-trpa1-and-trpm8-agonists-on-swallowing-dysfunction-associated-with-aging-and-neurological-diseases
#16
D Alvarez-Berdugo, L Rofes, V Arreola, A Martin, L Molina, P Clavé
BACKGROUND: Oropharyngeal sensory impairment is a potential target to treat swallowing dysfunction in patients with oropharyngeal dysphagia (OD). AIM: To assess the therapeutic effect of stimulating oropharyngeal sensory afferents with TRPV1, TRPA1, or TRPM8 agonists vs increasing bolus viscosity in older and neurologic patients with OD by comparing four studies of similar experimental design. METHODS: Swallow function of 142 older patients with impaired safety of swallow at nectar ([50-350] mPa·s) viscosity was evaluated with videofluoroscopy (VFS) while treated with TRPV1 (150 μmol/L), TRPV1/A1 (150 μmol/L and 1 mmol/L), or TRPM8 (1 mmol/L or 10 mmol/L) agonists or modified starch (MS) at spoon thick viscosity (>1750 mPa·s)...
August 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28790335/involvement-of-transient-receptor-potential-cation-channel-member-a1-activation-in-the-irritation-and-pain-response-elicited-by-skin-lightening-reagent-hydroquinone
#17
Yan Tai, Chuan Wang, Zhihua Wang, Yi Liang, Junying Du, Dongwei He, Xiaoyan Fan, Sven-Eric Jordt, Boyi Liu
Hydroquinone (HQ) is one of the most frequently used and effective skin-lightening products to treat skin hyperpigmentation disorders, including postinflammatory hyperpigmentation, melasma and solar lentigines. HQ is also widely used in cosmetic products for skin whitening. However, HQ treatment can evoke substantial skin irritation, a side effect that remains poorly understood. Here we demonstrate that HQ is an activator of the peripheral irritant receptor transient receptor potential (TRP) cation channel member A1 (TRPA1)...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768647/activation-of-transient-receptor-potential-melastatin-subtype-8-attenuates-cold-induced-hypertension-through-ameliorating-vascular-mitochondrial-dysfunction
#18
Shiqiang Xiong, Bin Wang, Shaoyang Lin, Hexuan Zhang, Yingsha Li, Xing Wei, Yuanting Cui, Xiao Wei, Zongshi Lu, Peng Gao, Li Li, Zhigang Zhao, Daoyan Liu, Zhiming Zhu
BACKGROUND: Environmental cold-induced hypertension is common, but how to treat cold-induced hypertension remains an obstacle. Transient receptor potential melastatin subtype 8 (TRPM8) is a mild cold-sensing nonselective cation channel that is activated by menthol. Little is known about the effect of TRPM8 activation by menthol on mitochondrial Ca(2+) homeostasis and the vascular function in cold-induced hypertension. METHODS AND RESULTS: Primary vascular smooth muscle cells from wild-type or Trpm8(-/-) mice were cultured...
August 2, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28767579/the-identification-of-the-trpm8-channel-on-primary-culture-of-human-nasal-epithelial-cells-and-its-response-to-cooling
#19
Shao-Cheng Liu, Hsuan-Hsuan Lu, Hueng-Chuen Fan, Hsing-Won Wang, Hang-Kang Chen, Fei-Peng Lee, Chong-Jen Yu, Yueng-Hsiang Chu
BACKGROUND: It has been proposed that the transient receptor potential (TRP) channel Melastatin 8 (TRPM8) is a cold-sensing TRP channel. However, its presence and its role in the nasal cavity have not yet been fully studied. METHODS: Immunohistology was used to study TRPM8 receptors in both the nasal mucosa tissue and the primary cultures of human nasal cells. Cells from primary cultures were immunostained with antibodies to TRPM8, mucin, cytokeratin (CK)-14, CK-18, and vimentin...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28766746/sensory-effects-of-transient-receptor-potential-channel-agonists-on-whole-mouth-saliva-extensional-rheology
#20
Jack William Houghton, Joachim Hans, Manuel Pesaro, Jakob Peter Ley, Guy Howard Carpenter, Gordon Proctor
The extensional rheology (ER) of saliva is a property associated with its ability to coat surfaces and is important for the maintenance of a normal mouth feeling. Transient receptor potential (TRP) channels are expressed in the oral cavity and this study investigated how the sensory effects of TRP channel agonists modify the ER of saliva. Healthy volunteers rinsed with solutions containing a TRP agonist. Unstimulated whole mouth saliva (WMS) was collected prior to rinsing and WMS was collected during the first and second minutes after the mouth rinse...
August 2017: Journal of Texture Studies
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