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Tao Liu, Yixiang Liao, Huangheng Tao, Jinmin Zeng, Gang Wang, Zhonghua Yang, Yongzhi Wang, Yu Xiao, Jiajie Zhou, Xinghuan Wang
Several studies have shown that transient receptor potential cation channel subfamily M member 8 (TRPM8), which has been regarded as a novel prostate-specific marker, serves a key role in processes such as the proliferation, viability and cell migration of prostate cancer cells. Efforts have been made to uncover the potential role of targeting TRPM8 in the management of prostate cancer; it has been verified that TRPM8-targeted blockade, either by RNA interference-mediated depletion or specific TRPM8 inhibitors, could reduce the rate of proliferation and proliferative fraction, and induce apoptosis in prostate cancer cells...
April 2018: Oncology Letters
Alfonso Reimúndez, Carlos Fernández-Peña, Guillermo García, Rubén Fernández, Purificación Ordás, Rosalía Gallego, José L Pardo-Vazquez, Victor Arce, Félix Viana, Rosa Señarís
The coupling of energy homeostasis to thermoregulation is essential to maintain homeothermy in changing external environments. We studied the role of the cold thermoreceptor TRPM8 in this interplay in mice of both sexes. We demonstrate that TRPM8 is required for a precise thermoregulation in response to cold, in fed and fasting. Trpm8-/- mice exhibited a fall of 0.7 °C in core body temperature (Tc) when housed at cold temperatures, and a deep hypothermia (below 30 °C) during food deprivation. In both situations TRPM8-deficiency induced an increase in tail heat loss...
March 12, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
J V Pergolizzi, R Taylor, J-A LeQuang, R B Raffa
WHAT IS KNOWN AND OBJECTIVE: Menthol has been used as a non-opioid pain reliever since ancient times. A modern understanding of its molecular mechanism of action could form the basis for generating targets for discovery of novel non-opioid analgesic drugs. METHODS: The PubMed database was queried using search words related to menthol, pain and analgesia. The results were limited to relevant preclinical studies and clinical trials and reviews published in English during the past 5 years, which yielded 31 reports...
March 10, 2018: Journal of Clinical Pharmacy and Therapeutics
Alberto González, Claudio A Sáez, Bernardo Morales, Alejandra Moenne
The existence of functional Transient Receptor Potential (TRP) channels was analyzed in Ectocarpus siliculosus using agonists of human TRPs and specific antagonists of TRPA1, TRPC5, TRPM8 and TRPV; intracellular calcium was detected for 60 min. Increases in intracellular calcium were observed at 13, 29, 39 and 50-52 min, which appeared to be mediated by the activation of TRPM8/V1 at 13 min, TRPV1 at 29 min, TRPA1/V1 at 39 min and TRPA1/C5 at 50-52 min. In addition, intracellular calcium increases appear to be due to extracellular calcium entry, not requiring protein kinase activation...
March 2, 2018: Plant Physiology and Biochemistry: PPB
Won Jai Jung, Sang Yeub Lee, Sue In Choi, Byung-Keun Kim, Eun Joo Lee, Kwang Ho In, Min-Goo Lee
Airway sensory nerves are known to express several receptors and channels that are activated by exogenous and endogenous mediators that cause coughing. Toll-like receptor (TLR) s are expressed in nociceptive neurons and play an important role in neuroinflammation. However, there have been very few studies of TLR expression in lung-derived sensory neurons or their relevance to respiratory symptoms such as cough. We used the bleomycin-induced pulmonary fibrosis model to investigate the change in TLR expression in pulmonary neurons and the association of TLRs with transient receptor potential (TRP) channels in pulmonary neurons...
2018: PloS One
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
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
March 6, 2018: Scientific Reports
Azusa Majikina, Kenji Takahashi, Shigeru Saito, Makoto Tominaga, Toshio Ohta
Pulegone, one of avian repellents, is used to prevent the economic loss caused by birds. Chemical repellents often evoke unpleasant sensations and sensory irritation resulting in avoidance under some circumstances. It is recognized that some TRP channels expressing sensory neurons are related to nociception. Here we determined the molecular mechanisms of the repellent action of pulegone using isolated chicken sensory neurons and heterologous expression system. Pulegone increased the intracellular Ca2+ concentration ([Ca2+ ]i ) in chicken sensory neurons...
February 28, 2018: Biochemical Pharmacology
Kunsala T D S Yapa, Jennifer Deuis, Amelia A Peters, Paraic A Kenny, Sarah J Roberts-Thomson, Irina Vetter, Gregory R Monteith
AIMS: To assess levels of the calcium permeable transient receptor potential cation channel, subfamily melastatin, member 8 (TRPM8) in breast cancer molecular subtypes and to assess the consequences of TRPM8 pharmacological inhibition with AMTB (an inhibitor of TRPM8) on breast cancer cell lines. MATERIALS AND METHODS: Cell viability and migration of breast cancer cells was determined using MTS assays and wound healing assays, respectively. RNA-Seq analysis of breast tumours and qPCR in breast cancer cell lines were used to assess mRNA levels of ion channels...
February 26, 2018: Life Sciences
Carmen De Caro, Roberto Russo, Carmen Avagliano, Claudia Cristiano, Antonio Calignano, Andrea Aramini, Gianluca Bianchini, Marcello Allegretti, Laura Brandolini
BACKGROUND AND PURPOSE: Transient receptor potential (TRP) channels are a superfamily of non-selective cation permeable channels involved in peripheral sensory signalling. Animal studies have shown that several TRPs are relevant players in pain modulation. Among them, the TRP Melastatin8 (TRPM8) has elicited more interest for its controversial role in nociception. This channel, expressed by a subpopulation of sensory neurons in dorsal root ganglia (DRG) and trigeminal ganglia (TG), is activated by cold temperatures and cooling agents...
February 27, 2018: British Journal of Pharmacology
Patrick Beukema, Katherine L Cecil, Elena Peterson, Victor R Mann, Megumi Matsushita, Yoshio Takashima, Saket Navlakha, Alison L Barth
Somatosensation is a complex sense mediated by more than a dozen distinct neural subtypes in the periphery. Although pressure and touch sensation have been mapped to primary somatosensory cortex in rodents, it has been controversial whether pain and temperature inputs are also directed to this area. Here we use a well-defined somatosensory modality, cool sensation mediated by peripheral TrpM8-receptors, to investigate the neural substrate for cool perception in the mouse neocortex. Using activation of cutaneous TrpM8 receptor-expressing neurons, we identify candidate neocortical areas responsive for cool sensation...
February 26, 2018: Journal of Comparative Neurology
Verneri Anttila, Maija Wessman, Mikko Kallela, Aarno Palotie
Genetics of migraine has recently undergone a major shift, moving in the space of a few years from having only a few known genes for rare Mendelian forms to 47 known common variant loci affecting the susceptibility of the common forms of migraine. This has largely been achieved by rapidly increasing sample sizes for genomewide association studies (GWAS), soon to be followed by the first wave of large-scale exome-sequencing studies. The large number of detected loci, chief among them TRPM8, PRDM16, and LRP1, have enabled a number of in silico analyses, which have shed light on the functional and tissue-level aspects of the common risk variants for migraine, including evidence for involvement of both vascular and neuronal mechanisms...
2018: Handbook of Clinical Neurology
Michael Camilleri
This is an editorial summarizing recent new developments in visceral analgesics. This promising field is important as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors through biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs...
February 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Naoki Aizawa, Yoshikazu Fujimori, Jun-Ichi Kobayashi, Osamu Nakanishi, Hideaki Hirasawa, Haruki Kume, Yukio Homma, Yasuhiko Igawa
AIMS: Transient receptor potential melastatin 8 (TRPM8) is proposed to be a promising therapeutic target for hypersensitive bladder disorders. We examined the effects of KPR-2579, a novel selective TRPM8 antagonist, on body temperature and on mechanosensitive bladder single-unit afferent activities (SAAs) provoked by intravesical acetic acid (AA) instillation in rats. METHODS: Female Sprague-Dawley rats were used. Effects of cumulative intravenous (i.v.) administrations of KPR-2579 (0...
February 21, 2018: Neurourology and Urodynamics
Wang Zheng, Ruiqi Cai, Laura Hofmann, Vasyl Nesin, Qiaolin Hu, Wentong Long, Mohammad Fatehi, Xiong Liu, Shaimaa Hussein, Tim Kong, Jingru Li, Peter E Light, Jingfeng Tang, Veit Flockerzi, Leonidas Tsiokas, Xing-Zhen Chen
Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function analyses revealed similar N-C interaction in TRPP2 as well as TRPM8/-V1/-C4 via highly conserved tryptophan and lysine/arginine residues...
February 6, 2018: Cell Reports
Marilin Ivask, Sander Pajusalu, Ene Reimann, Sulev Kõks
Wolfram syndrome is caused by mutations in the WFS1 gene. WFS1 protein dysfunction results in a range of neuroendocrine syndromes and is mostly characterized by juvenile-onset diabetes mellitus and optic atrophy. WFS1 has been shown to participate in membrane trafficking, protein processing and Ca2+ homeostasis in the endoplasmic reticulum. Aim of the present study was to find the transcriptomic changes influenced by WFS1 in the hypothalamus and hippocampus using RNA-sequencing. The WFS1-deficient mice were used as a model system to analyze the changes in transcriptional networks...
February 3, 2018: Neuroscience
J B Lindström, N T Pierce, M I Latz
Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences...
October 2017: Biological Bulletin
Robson Cristiano Lillo Vizin, Anna Carolina Parracho Motzko-Soares, Giovana Marchini Armentano, Debora T Ishikawa, Ariovaldo Pereira Cruz-Neto, Daniel Carneiro Carrettiero, Maria Camila Almeida
In this study, we aimed at evaluating the influence of daily repeated menthol treatments on body mass and thermoregulatory effectors in Wistar rats, considering that menthol is a TRPM8 channel agonist that mimics cold sensation and activates thermoregulatory cold-defense mechanisms in mammals, promoting hyperthermia and increasing energy expenditure, and has been suggested as an anti-obesity drug. Male Wistar rats were topically treated with 5% menthol for 3 or 9 consecutive days, while body mass, food intake, abdominal temperature, metabolism, cutaneous vasoconstriction and thermal preference were measured...
December 21, 2017: Journal of Applied Physiology
João F Neves Neto, Zaira Palomino, Ingrid K Mizuno Watanabe, Wilson F Aguiar, Jose O Medina-Pestana, Roberto Soler
AIMS: The objective of this study was to evaluate the expression of bladder receptors in patients with defunctionalized bladder (DB) and to assess voiding behavior after refunctionalization. METHODS: A total of 68 pretransplant patients were divided in two groups: DB (diuresis <300 mL/24 h; n = 33) and NDB (non-DB; diuresis ≥300 mL/24 h; n = 35). A sample of mucosa and detrusor at the site of the future ureteral implantation was collected...
January 22, 2018: Neurourology and Urodynamics
I Weyer-Menkhoff, M C Thrun, J Lötsch
BACKGROUND: Pain in response to noxious cold has a complex molecular background probably involving several types of sensors. A recent observation has been the multimodal distribution of human cold pain thresholds. This study aimed at analysing reproducibility and stability of this observation and further exploration of data patterns supporting a complex background. METHOD: Pain thresholds to noxious cold stimuli (range 32-0 °C, tonic: temperature decrease -1 °C/s, phasic: temperature decrease -8 °C/s) were acquired in 148 healthy volunteers...
January 16, 2018: European Journal of Pain: EJP
Leigh A Nattkemper, Hong Liang Tey, Rodrigo Valdes-Rodriguez, Helen Lee, Nicholas K Mollanazar, Christian Albornoz, Kristen M Sanders, Gil Yosipovitch
To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete transcriptome in skin from paired itchy, lesional and non-itchy, non-lesional skin biopsies from 25 atopic dermatitis (AD) and 25 psoriasis patients and site-matched biopsies from 30 healthy controls. This analysis identified 18,000 differentially expressed genes common between itchy atopic and psoriatic skin compared to healthy skin. Of those, almost 2,000 genes were differentially expressed between itchy and non-itchy skin in atopic and psoriatic subjects...
January 6, 2018: Journal of Investigative Dermatology
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