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TRPV1 receptor agonist

Kaiyu Qian, Gang Wang, Rui Cao, Tao Liu, Guofeng Qian, Xinyuan Guan, Zhongqiang Guo, Yu Xiao, Xinghuan Wang
Capsaicin (CAP), a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1), has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa) are available, but accompanied by unfavorable outcomes. Previous studies reported a potential clinical effect of CAP to prevent BCa tumorigenesis. However, its underlying molecular mechanism still remains unknown. Our transcriptome analysis suggested a close link among calcium signaling pathway, cell cycle regulation, ROS metabolism and FOXO signaling pathway in BCa...
October 21, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Cassandra E Deering-Rice, Chris Stockmann, Erin G Romero, Zhenyu Lu, Darien Shapiro, Brian L Stone, Bernhard Fassl, Flory Nkoy, Derek A Uchida, Robert M Ward, John M Veranth, Christopher A Reilly
Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of TRPV1 would be uniquely responsive to insoluble coal fly ash compared to the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1 I315M and T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles, due to reduced translation of protein and an apparent role for I585 in activation by particles...
October 7, 2016: Journal of Biological Chemistry
W Ma, B St-Jacques, U Rudakou, Y N Kim
BACKGROUND: Persistent peripheral sensitization contributes to chronic pain. Plasticity of nociceptive dorsal root ganglion (DRG) neurons (nociceptors) induced by pro-inflammatory mediators contributes to sensitization. Prostaglandin E2 (PGE2) enriched in injured tissues is known not only directly to sensitize DRG neurons, but also to potentiate sensitizing effects of other pain mediators such as capsaicin and its receptor transient receptor potential vanilloid-1 (TRPV1). It remains unknown whether PGE2 potentiates TRPV1 activity by stimulating its synthesis, cell surface and axonal trafficking in DRG neurons...
October 14, 2016: European Journal of Pain: EJP
Masayuki Saito, Takeshi Yoneshiro, Mami Matsushita
Since the recent re-discovery of brown adipose tissue (BAT) in adult humans, this thermogenic tissue has attracted increasing interest. The inverse relationship between the BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. Cold exposure activates and recruits BAT in association with increased energy expenditure and decreased body fatness. The stimulatory effects of cold are mediated through transient receptor potential channels (TRP), most of which are also chemesthetic receptors for various food ingredients...
August 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
Kazuaki Yamagata, Mitsutaka Sugimura, Miki Yoshida, Shinichi Sekine, Akiyo Kawano, Aiko Oyamaguchi, Hiroharu Maegawa, Hitoshi Niwa
Several trigeminal pain disorders show sex differences, and high levels of estrogens may underlie these differences. The interaction between transient receptor potential vanilloid 1 (TRPV1) and anoctamin 1 (ANO1) plays an important role in peripheral nociception. However, whether TRPV1 and ANO1 are involved in estrogen-modulated trigeminal pain sensitivity is unclear. In this study, we examined 17β-estradiol (E2) modulation of nociception through behavioral and immunohistological experiments following application of capsaicin (Cap), a selective TRPV1 agonist, onto the ocular surface in ovariectomized rats treated with high- (HE) or low-dose E2 (LE) for 2 days...
September 30, 2016: Endocrinology
Imre Farkas, Csaba Vastagh, Erzsébet Farkas, Flóra Bálint, Katalin Skrapits, Erik Hrabovszky, Csaba Fekete, Zsolt Liposits
Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM-5 μM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R...
2016: Frontiers in Cellular Neuroscience
Carl M Hurt, Yao Lu, Creed M Stary, Honit Piplani, Bryce A Small, Travis J Urban, Nir Qvit, Garrett J Gross, Daria Mochly-Rosen, Eric R Gross
BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) mediates cellular responses to pain, heat, or noxious stimuli by calcium influx; however, the cellular localization and function of TRPV1 in the cardiomyocyte is largely unknown. We studied whether myocardial injury is regulated by TRPV1 and whether we could mitigate reperfusion injury by limiting the calcineurin interaction with TRPV1. METHODS AND RESULTS: In primary cardiomyocytes, confocal and electron microscopy demonstrates that TRPV1 is localized to the mitochondria...
2016: Journal of the American Heart Association
László Pecze, Walter Blum, Thomas Henzi, Beat Schwaller
Sensory neuron subpopulations as well as breast and prostate cancer cells express functional transient receptor potential vanilloid type 1 (TRPV1) ion channels; however little is known how TRPV1 activation leads to biological responses. Agonist-induced activation of TRPV1 resulted in specific spatiotemporal patterns of cytoplasmic Ca(2+) signals in breast and prostate cancer-derived cells. Capsaicin (CAPS; 50μM) evoked intracellular Ca(2+) oscillations and/or intercellular Ca(2+) waves in all cell lines. As evidenced in prostate cancer Du 145 cells, oscillations were largely dependent on the expression of functional TRPV1 channels in the plasma membrane, phospholipase C activation and on the presence of extracellular Ca(2+) ions...
September 20, 2016: Biochimica et Biophysica Acta
Ricardo Ramírez-Barrantes, Ivanny Marchant, Pablo Olivero
Aging induces physical deterioration, loss of the blood brain barrier, neuronal loss-induced mental and neurodegenerative diseases. Hypotalamus-hypophysis-gonad axis aging precedes symptoms of menopause or andropause and is a major determinant of sensory and cognitive integrated function. Sexual steroids support important functions, exert pleiotropic effects in different sensory cells, promote regeneration, plasticity and health of the nervous system. Their diminution is associated with impaired cognitive and mental health and increased risk of neurodegenerative diseases...
August 2016: Neural Regeneration Research
Naoki Tsuno, Akira Yukimasa, Osamu Yoshida, Yusuke Ichihashi, Takatsugu Inoue, Tatsuhiko Ueno, Hiroki Yamaguchi, Hidetoshi Matsuda, Satoko Funaki, Natsue Yamanada, Miki Tanimura, Daiki Nagamatsu, Yoko Nishimura, Tetsuji Ito, Masahiko Soga, Narumi Horita, Miyuki Yamamoto, Mikie Hinata, Masayuki Imai, Yasuhide Morioka, Toshiyuki Kanemasa, Gaku Sakaguchi, Yasuyoshi Iso
A novel series of 2',4'-dimethyl-[4,5'-bithiazol]-2-yl amino derivatives were found by high throughput screening of the TRPV4 receptor, at which these compounds showed competitive antagonist potential against 4α-phorbol 12,13-didecanoate (4αPDD) as the selective TRPV4 agonist and showed excellent selectivity for TRPV1, N-type and L-type calcium ion channels, but poor ADME profile. In our SAR strategy, we found that the lead molecule 1 also having the unique 3-oxa-9-azabicyclo [3.3.1] nonan-7-one on the right part showed potent TRPV4 antagonist activity, good solubility at pH 6...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
Katsuya Ohbuchi, Yoshikazu Mori, Kazuo Ogawa, Eiji Warabi, Masahiro Yamamoto, Takatsugu Hirokawa
Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel and a multimodal sensor protein. Since the precise structure of TRPV1 was obtained by electron cryo-microscopy, the binding mode of representative agonists such as capsaicin and resiniferatoxin (RTX) has been extensively characterized; however, detailed information on the binding mode of other vanilloids remains lacking. In this study, mutational analysis of human TRPV1 was performed, and four agonists (capsaicin, RTX, [6]-shogaol and [6]-gingerol) were used to identify amino acid residues involved in ligand binding and/or modulation of proton sensitivity...
2016: PloS One
Igor A Schepetkin, Svetlana V Kushnarenko, Gulmira Özek, Liliya N Kirpotina, Pritam Sinharoy, Gulzhakhan A Utegenova, Karime T Abidkulova, Temel Özek, Kemal Hüsnü Can Başer, Anastasia R Kovrizhina, Andrei I Khlebnikov, Derek S Damron, Mark T Quinn
Essential oils were obtained by hydrodistillation of the umbels+seeds and stems of Ferula akitschkensis (FAEOu/s and FAEOstm, respectively) and analyzed by gas chromatography and gas chromatography-mass spectrometry. Fifty-two compounds were identified in FAEOu/s; the primary components were sabinene, α-pinene, β-pinene, terpinen-4-ol, eremophilene, and 2-himachalen-7-ol, whereas the primary components of FAEOstm were myristicin and geranylacetone. FAEOu/s, β-pinene, sabinene, γ-terpinene, geranylacetone, isobornyl acetate, and (E)-2-nonenal stimulated [Ca(2+)]i mobilization in human neutrophils, with the most potent being geranylacetone (EC50 = 7...
September 28, 2016: Journal of Agricultural and Food Chemistry
Vincenzo Carnevale, Tibor Rohacs
Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective, Ca(2+) permeable cation channel activated by noxious heat, and chemical ligands, such as capsaicin and resiniferatoxin (RTX). Many compounds have been developed that either activate or inhibit TRPV1, but none of them are in routine clinical practice. This review will discuss the rationale for antagonists and agonists of TRPV1 for pain relief and other conditions, and strategies to develop new, better drugs to target this ion channel, using the newly available high-resolution structures...
August 23, 2016: Pharmaceuticals
Jessica A Fawley, Mackenzie E Hofmann, Michael C Andresen
UNLABELLED: Most craniosensory afferents have unmyelinated axons expressing TRP Vanilloid 1 (TRPV1) receptors in synaptic terminals at the solitary tract nucleus (NTS). Neurotransmission from these synapses is characterized by substantial asynchronous EPSCs following action potential-synched EPSCs and high spontaneous rates that are thermally sensitive. The present studies blocked voltage-activated calcium channels (CaV) using the nonselective CaV blocker Cd(2+) or the specific N-type blocker ω-conotoxin GVIA to examine the calcium dependence of the synchronous, asynchronous, spontaneous, and thermally gated modes of release...
August 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ramona Lehmann, Hanns Hatt, Christoph van Thriel
One important function of the peripheral nervous system is the detection of noxious chemicals in the environment as well as the recognition of tissue damage throughout the body. Transient receptor potential (TRP) ion channels are able to sense a multitude of signaling factors involved in these processes. Via the sensory ganglia these sentinels convey information to the central nervous system, where perceptions of nociception or sensory irritation are generated. From the 28 members of the 6 subfamilies present in mammals, researchers in toxicology paid special attention to TRPA1 and TRPV1 channels...
August 18, 2016: Neurotoxicology
Xiaoqun Zhang, Ning Yao, Karima Chergui
Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABAA receptor agonist muscimol was recently found to trigger a long-lasting depression of glutamatergic synaptic transmission in the NAc of adolescent mice, but the mechanisms that underlie this novel form of LTD were not studied. Here we examined the effect of muscimol applied in the perfusion solution on the amplitude of field excitatory postsynaptic potentials/population spikes (fEPSP/PSs) in mouse brain slices...
September 2016: Learning & Memory
Dorothy Cimino Brown
Control of chronic pain is frequently inadequate or can be associated with debilitating side effects. Ablation of certain nociceptive neurons, while retaining all other sensory modalities and motor function, represents a new therapeutic approach to controlling severe pain while avoiding off-target side effects. transient receptor potential cation channel subfamily V member 1 (TRPV1) is a calcium permeable nonselective cation channel expressed on the peripheral and central terminals of small-diameter sensory neurons...
August 11, 2016: Pharmaceuticals
Manish K Madasu, Bright N Okine, Weredeselam M Olango, Kieran Rea, Róisín Lenihan, Michelle Roche, David P Finn
Negative affective state has a significant impact on pain, and genetic background is an important moderating influence on this interaction. The Wistar-Kyoto (WKY) inbred rat strain exhibits a stress-hyperresponsive, anxiety/depressive-like phenotype and also displays a hyperalgesic response to noxious stimuli. Transient receptor potential subfamily V member 1 (TRPV1) within the midbrain periaqueductal grey (PAG) plays a key role in regulating both aversive and nociceptive behaviour. In the present study, we investigated the role of TRPV1 in the sub-columns of the PAG in formalin-evoked nociceptive behaviour in WKY versus Sprague-Dawley (SD) rats...
August 9, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Michał Biernacki, Elżbieta Skrzydlewska
Endocannabinoids belong to a group of ester, ether and amide derivatives of fatty acids, which are endogenous ligands of receptors CB1, CB2, TRPV1 and GPR55 that are included in the endocannabinoid system of the animal organism. The best known endocannabinoids are: N-arachidonylethanolamide called anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They occur in all organisms, and their highest level is observed in the brain. In this review the mechanisms of synthesis and degradation of both AEA and 2-AG are shown...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
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