DOCSLIB.ORG

Regulation of TRP Channels by Steroids

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

General and Comparative Endocrinology xxx (2014) xxx–xxx Contents lists available at ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen Review Regulation of TRP channels by steroids: Implications in physiology and diseases ⇑ Ashutosh Kumar, Shikha Kumari, Rakesh Kumar Majhi, Nirlipta Swain, Manoj Yadav, Chandan Goswami School of Biology, National Institute of Science Education and Research, Sachivalaya Marg, Bhubaneswar, Orissa 751005, India article info abstract Article history: While effects of different steroids on the gene expression and regulation are well established, it is proven Available online xxxx that steroids can also exert rapid non-genomic actions in several tissues and cells. In most cases, these non-genomic rapid effects of steroids are actually due to intracellular mobilization of Ca2+- and other ions Keywords: suggesting that Ca2+ channels are involved in such effects. Transient Receptor Potential (TRP) ion TRP channels channels or TRPs are the largest group of non-selective and polymodal ion channels which cause Ca2+- Steroids influx in response to different physical and chemical stimuli. While non-genomic actions of different Non-genomic action of steroids steroids on different ion channels have been established to some extent, involvement of TRPs in such Ca2+-influx functions is largely unexplored. In this review, we critically analyze the literature and summarize how Expression different steroids as well as their metabolic precursors and derivatives can exert non-genomic effects by acting on different TRPs qualitatively and/or quantitatively. Such effects have physiological repercus- sion on systems such as in sperm cells, immune cells, bone cells, neuronal cells and many others. Different TRPs are also endogenously expressed in diverse steroid-producing tissues and thus may have importance in steroid synthesis as well, a process which is tightly controlled by the intracellular Ca2+ con- centrations. Tissue and cell-specific expression of TRP channels are also regulated by different steroids. Understanding of the crosstalk between TRP channels and different steroids may have strong significance in physiological, endocrinological and pharmacological context and in future these compounds can also be used as potential biomedicine. Ó 2014 Elsevier Inc. All rights reserved. 1. Introduction receptors and ion channels involved in such responses are largely unknown. Nevertheless, identification of molecular candidates Steroid actions can be both genomic and non-genomic (i.e., involved in rapid steroid signaling events and understanding of rapid effects produced within minutes and which are independent the signaling events involved in such processes are important from of transcriptional or translational stimulation). In contrast to the a physiological, pharmacological and clinical perspective. In this well-established genomic effects, these non-genomic and rapid context, Transient Receptor Potential (TRP) ion channels (TRPs) effects of steroids are poorly understood, although such effects are relevant. have been noted in several systems including neurons. For exam- TRPs are a group of non-selective ion channels which mediate ple, very rapid effects of several neurosteroids on the neuronal sys- the transmembrane flux of Ca2+ (and other cations too) down an tem is well established. Notably, it has been observed that fast and electrochemical gradient, thereby increasing the intracellular Ca2+ non-genomic actions of steroids are dose-dependent, often revers- and Na+ concentration and causing cell depolarization. TRP chan- ible, stereo-specific and can be blocked by other signaling com- nels were first discovered in a Drosophila trp mutant, which had pounds suggesting that these steroids initiate specific biological a modified response to light (Minke, 1977; Montell et al., 1985). responses through specific signaling cascades (Gu and Moss, Subsequently members of the TRP family have been identified in 1996; Falkenstein et al., 2000). While a handful of reports suggest vertebrates, and other invertebrates and in lower eukaryotes such that these fast and non-genomic effects of steroids originate at the as yeast and fungi. However, so far TRPs or their exact homologs plasma membrane, the molecular mechanisms and the signaling have not been detected in plants. TRPs are classified on the basis events are not well understood. The molecular identities of the of their sequence homology and by the presence of specific signa- ture domains and motifs such as the TRP-domain, TRP-box motifs, ankyrin repeats, etc. (Clapham, 2003; Nilius and Owsianik, 2011). ⇑ Corresponding author. E-mail address: [email protected] (C. Goswami). The primary structure of all TRPs consists of six transmembrane http://dx.doi.org/10.1016/j.ygcen.2014.10.004 0016-6480/Ó 2014 Elsevier Inc. All rights reserved. Please cite this article in press as: Kumar, A., et al. Regulation of TRP channels by steroids: Implications in physiology and diseases. Gen. Comp. Endocrinol. (2014), http://dx.doi.org/10.1016/j.ygcen.2014.10.004 2 A. Kumar et al. / General and Comparative Endocrinology xxx (2014) xxx–xxx regions with a pore domain between the fifth and sixth transmem- mRNA and protein levels as well as duodenal TRPV6 expression brane region and both the N- and C-termini are intracellular. Based in rats (van Abel et al., 2002, 2003). In mice TRPV6 expression on amino acid sequence, homology with other TRP channels, and was induced after 17b-estradiol treatment (Lee and Jeung, 2007) the presence of specific structural features, the TRPs have been and in pregnant rat, expression of TRPV6 transcription appeared classified into 7 subfamilies, namely, TRPC (Canonical), TRPV to be solely controlled by progesterone (Lee et al., 2009). Estrogen (Vanilloid), TRPM (Melastatin), TRPA (Ankyrin), TRPP (Polycystin), in particular has also been shown to induce the expression of TRPML (Mucolipin) and TRPN (No Mechanoreceptor Potential C, TRPV1 channel in rats (Yan et al., 2007). In MCF-7 which is a breast NOMPC). cancer cell line, ERa has been shown to regulate the expression of In animals, TRP channels are ubiquitously expressed in almost TRPM8 (Chodon et al., 2010). all cell types and tissues, albeit at different levels. However, Often the expressions of different TRP channels in a given involvement of TRP channels in physiological functions and sen- tissue/cell are tightly controlled by the serum levels of different sory processes are relevant in multi-cellular as well as in unicellu- steroid hormones. For example, female sex hormones E2 and P4 lar organisms also. Most of the TRPs are selectively activated by alone or in combination can modulate the transcription of trp specific ligands and are polymodal in nature (Baez-Nieto et al., genes involved in physiological functions linked to pregnancy. 2011). TRP channels are regulated by multiple stimuli, both phys- The uterine expression of TRPV6 during the estrous cycle in ical and chemical and a few members of TRPs, namely TRPV1, rodents is modulated by steroid hormones and TRPV6 transcripts TRPV2, TRPV3, TRPV4, TRPM3, TRPM8, TRPA1 are thermosensitive. in the rat uterus is highly up-regulated by P4 at diestrus (Kim In most cases the chemical ligands are hydrophobic in nature and et al., 2006), while in mouse uterus TRPV6 mRNA is up-regulated several endogenous hydrophobic compounds (such as different lip- by E2 at estrus (Lee and Jeung, 2007). Uterine TRPV6 has increased ids) have been reported to activate or inhibit TRP channels (Holzer, expression during implantation and just prior to birth while it 2011). The complex polymodal regulation of TRP channels by intra- declines sharply following birth and during lactation, and is mainly cellular as well as extracellular components such as, specific lipids, regulated by serum concentrations of P4 or E2 in rat and mouse pH, ROS, NO, metal ions, interacting proteins, etc. and the multiple respectively (Lee et al., 2009). In rodents TRPV6 expression in the routes of regulation by phosphorylation-dephosphorylation and placenta initially follows the pattern of uterine expression, with other post-translational modifications, suggest that these channels an induction in the middle of gestation but not at the end of gesta- integrate multiple signaling events at the plasma membrane. In tion (Lee and Jeung, 2007). The species-specific regulation of TRPV6 this context, TRPs have been investigated for rapid signaling med- transcription in the uterus and placenta may be a consequence of iated by different steroids and may be an important group of the uterine calcium ion concentration required for successful molecular targets for the fast and non-genomic actions of different implantation of embryo and in rats P4 and PRs are important while steroids. Reports also suggest that expressions of TRPs are also con- in mice E2 and ERs are regulatory (Lee et al., 2009). trolled by different steroids as long-term effects. The crosstalk Several other TRP channels are also regulated by E2 and P4. For between steroids and TRPs may have crucial implications in sev- example, both E2 and P4 are involved in the regulation of trpm2 eral spheres such as in clinical, pharmacological, endocrinology, gene during the oestrous cycle of female rats. Changes in TRPM2 food safety, species conservation and several other aspects. The expression in stromal cells of the myometrium and endometrium present review will present the importance of TRPs in the signaling of mature rats during oestrous
Recommended publications
  • Pepperspray, CS, & Other 'Less-Lethal' Weapons

    Pepperspray, CS, & Other 'Less-Lethal' Weapons

    CONTENTS: Protective Measures: p.26-27 Pepperspray: p.2-9, 14-15 Chemical Data Table: p.30 CS/CN: p.10-16 Risk Groups: p.14-15 When to do what / Other Gas Types: p. 12 Asthma: p.14 treatment algorithm: p.4 Rubber Bullets: p.19-21 Nightsticks/Batons: p.17 LAW: p.6 Concussion Grenades: p.22 CR: p.12 VOFIBA: p.7 Fear: p.24 CA: p.12 Making Remedies: p.13 Tasers: p.18 DM: p.12 Sample Card for Handing Out: Shamelessly adapted from the Black Cross Radical Health Collective, www.blackcrosscollective.org If your condition is worsening, go to an emergency room. Basic preparations: Stick with your buddy. Pepperspray, CS, & Other Work with an affinity group. Bring water. Vulnerable people like asthmatics may want to “Less-Lethal” Weapons (your logo here) avoid chemical weapons. You must remove small children from the area BEFORE Used by Rioting Police to Suppress Dissent chemical weapons are used. Check out our w h e n P o l i t r i c k s & Te l e v i s i o n f a i l t o d o s o . website <www.---.org> for lots more info on how to prepare. v3.3 Useful Numbers: Serious injuries: If you don’t know how to treat Medical Emergency: 911 an injury, get a medic, or call 911. Don’t treat Copwatch: 123-4560 someone if you don’t know how. If you are Convergence Ctr Aid Station:123-4567 injured by the police, get to a nurse practitioner, Aftercare Clinic: 123-4568 physician’s assistant, or doctor immediately Legal Team: 123-4565 and have your injury documented in case you Public Defenders: 123-4569 decide to sue.
  • TRPM8 Activation by Menthol, Icilin, and Cold Is Differenially Modulated by Intracellular Ph

    TRPM8 Activation by Menthol, Icilin, and Cold Is Differenially Modulated by Intracellular Ph

    5364 • The Journal of Neuroscience, June 9, 2004 • 24(23):5364–5369 Cellular/Molecular TRPM8 Activation by Menthol, Icilin, and Cold Is Differentially Modulated by Intracellular pH David A. Andersson, Henry W. N. Chase, and Stuart Bevan Novartis Institute for Medical Sciences, London WC1E 6BN, United Kingdom TRPM8 is a nonselective cation channel activated by cold and the cooling compounds menthol and icilin (Peier et al., 2002). Here, we have used electrophysiology and the calcium-sensitive dye Fura-2 to study the effect of pH and interactions between temperature, pH, and the two chemical agonists menthol and icilin on TRPM8 expressed in Chinese hamster ovary cells. Menthol, icilin, and cold all evoked 2ϩ ϩ stimulus-dependent [Ca ]i responses in standard physiological solutions of pH 7.3. Increasing the extracellular [H ] from pH 7.3 to approximately pH 6 abolished responses to icilin and cold stimulation but did not affect responses to menthol. Icilin concentration– response curves were significantly shifted to the right when pH was lowered from 7.3 to 6.9, whereas those with menthol were unaltered in solutions of pH 6.1. When cells were exposed to solutions in the range of pH 8.1–6.5, the temperature threshold for activation was elevatedathigherpHanddepressedatlowerpH.Superfusingcellswithalowsubactivatingconcentrationoficilinormentholelevatedthe 2ϩ threshold for cold activation at pH 7.4, but cooling failed to evoke [Ca ]i responses at pH 6 in the presence of either agonist. In voltage-clamp experiments in which the intracellular pH was buffered to different levels, acidification reduced the current amplitude of icilin responses and shifted the threshold for cold activation to lower values with half-maximal inhibition at pH 7.2 and pH 7.6.
  • TRP Channel Transient Receptor Potential Channels

    TRP Channel Transient Receptor Potential Channels

    TRP Channel Transient receptor potential channels TRP Channel (Transient receptor potential channel) is a group of ion channels located mostly on the plasma membrane of numerous human and animal cell types. There are about 28 TRP channels that share some structural similarity to each other. These are grouped into two broad groups: Group 1 includes TRPC ("C" for canonical), TRPV ("V" for vanilloid), TRPM ("M" for melastatin), TRPN, and TRPA. In group 2, there are TRPP ("P" for polycystic) and TRPML ("ML" for mucolipin). Many of these channels mediate a variety of sensations like the sensations of pain, hotness, warmth or coldness, different kinds of tastes, pressure, and vision. TRP channels are relatively non-selectively permeable to cations, including sodium, calcium and magnesium. TRP channels are initially discovered in trp-mutant strain of the fruit fly Drosophila. Later, TRP channels are found in vertebrates where they are ubiquitously expressed in many cell types and tissues. TRP channels are important for human health as mutations in at least four TRP channels underlie disease. www.MedChemExpress.com 1 TRP Channel Inhibitors, Antagonists, Agonists, Activators & Modulators (-)-Menthol (E)-Cardamonin Cat. No.: HY-75161 ((E)-Cardamomin; (E)-Alpinetin chalcone) Cat. No.: HY-N1378 (-)-Menthol is a key component of peppermint oil (E)-Cardamonin ((E)-Cardamomin) is a novel that binds and activates transient receptor antagonist of hTRPA1 cation channel with an IC50 potential melastatin 8 (TRPM8), a of 454 nM. Ca2+-permeable nonselective cation channel, to 2+ increase [Ca ]i. Antitumor activity. Purity: >98.0% Purity: 99.81% Clinical Data: Launched Clinical Data: No Development Reported Size: 10 mM × 1 mL, 500 mg, 1 g Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg (Z)-Capsaicin 1,4-Cineole (Zucapsaicin; Civamide; cis-Capsaicin) Cat.
  • Snapshot: Mammalian TRP Channels David E

    Snapshot: Mammalian TRP Channels David E

    SnapShot: Mammalian TRP Channels David E. Clapham HHMI, Children’s Hospital, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA TRP Activators Inhibitors Putative Interacting Proteins Proposed Functions Activation potentiated by PLC pathways Gd, La TRPC4, TRPC5, calmodulin, TRPC3, Homodimer is a purported stretch-sensitive ion channel; form C1 TRPP1, IP3Rs, caveolin-1, PMCA heteromeric ion channels with TRPC4 or TRPC5 in neurons -/- Pheromone receptor mechanism? Calmodulin, IP3R3, Enkurin, TRPC6 TRPC2 mice respond abnormally to urine-based olfactory C2 cues; pheromone sensing 2+ Diacylglycerol, [Ca ]I, activation potentiated BTP2, flufenamate, Gd, La TRPC1, calmodulin, PLCβ, PLCγ, IP3R, Potential role in vasoregulation and airway regulation C3 by PLC pathways RyR, SERCA, caveolin-1, αSNAP, NCX1 La (100 µM), calmidazolium, activation [Ca2+] , 2-APB, niflumic acid, TRPC1, TRPC5, calmodulin, PLCβ, TRPC4-/- mice have abnormalities in endothelial-based vessel C4 i potentiated by PLC pathways DIDS, La (mM) NHERF1, IP3R permeability La (100 µM), activation potentiated by PLC 2-APB, flufenamate, La (mM) TRPC1, TRPC4, calmodulin, PLCβ, No phenotype yet reported in TRPC5-/- mice; potentially C5 pathways, nitric oxide NHERF1/2, ZO-1, IP3R regulates growth cones and neurite extension 2+ Diacylglycerol, [Ca ]I, 20-HETE, activation 2-APB, amiloride, Cd, La, Gd Calmodulin, TRPC3, TRPC7, FKBP12 Missense mutation in human focal segmental glomerulo- C6 potentiated by PLC pathways sclerosis (FSGS); abnormal vasoregulation in TRPC6-/-
  • Transient Receptor Potential Channels and Metabolism

    Transient Receptor Potential Channels and Metabolism

    Molecules and Cells Minireview Transient Receptor Potential Channels and Metabolism Subash Dhakal and Youngseok Lee* Department of Bio and Fermentation Convergence Technology, Kookmin University, BK21 PLUS Project, Seoul 02707, Korea *Correspondence: [email protected] https://doi.org/10.14348/molcells.2019.0007 www.molcells.org Transient receptor potential (TRP) channels are nonselective Montell, 2007). These cationic channels were first charac- cationic channels, conserved among flies to humans. Most terized in the vinegar fly, Drosophila melanogaster. While TRP channels have well known functions in chemosensation, a visual mechanism using forward genetic screening was thermosensation, and mechanosensation. In addition to being studied, a mutant fly showed a transient response to being sensing environmental changes, many TRP channels constant light instead of the continuous electroretinogram are also internal sensors that help maintain homeostasis. response recorded in the wild type (Cosens and Manning, Recent improvements to analytical methods for genomics 1969). Therefore, the mutant was named as transient recep- and metabolomics allow us to investigate these channels tor potential (trp). In the beginning, researchers had spent in both mutant animals and humans. In this review, we two decades discovering the trp locus with the germ-line discuss three aspects of TRP channels, which are their role transformation of the genomic region (Montell and Rubin, in metabolism, their functional characteristics, and their 1989). Using a detailed structural permeation property anal- role in metabolic syndrome. First, we introduce each TRP ysis in light-induced current, the TRP channel was confirmed channel superfamily and their particular roles in metabolism. as a six transmembrane domain protein, bearing a structural Second, we provide evidence for which metabolites TRP resemblance to a calcium-permeable cation channel (Mon- channels affect, such as lipids or glucose.
  • Trpa1) Activity by Cdk5

    Trpa1) Activity by Cdk5

    MODULATION OF TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY A, MEMBER 1 (TRPA1) ACTIVITY BY CDK5 A dissertation submitted to Kent State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy by Michael A. Sulak December 2011 Dissertation written by Michael A. Sulak B.S., Cleveland State University, 2002 Ph.D., Kent State University, 2011 Approved by _________________, Chair, Doctoral Dissertation Committee Dr. Derek S. Damron _________________, Member, Doctoral Dissertation Committee Dr. Robert V. Dorman _________________, Member, Doctoral Dissertation Committee Dr. Ernest J. Freeman _________________, Member, Doctoral Dissertation Committee Dr. Ian N. Bratz _________________, Graduate Faculty Representative Dr. Bansidhar Datta Accepted by _________________, Director, School of Biomedical Sciences Dr. Robert V. Dorman _________________, Dean, College of Arts and Sciences Dr. John R. D. Stalvey ii TABLE OF CONTENTS LIST OF FIGURES ............................................................................................... iv LIST OF TABLES ............................................................................................... vi DEDICATION ...................................................................................................... vii ACKNOWLEDGEMENTS .................................................................................. viii CHAPTER 1: Introduction .................................................................................. 1 Hypothesis and Project Rationale
  • (TRPM8) by Calcium-Rich Particulate Materials and Effects on Human

    (TRPM8) by Calcium-Rich Particulate Materials and Effects on Human

    Molecular Pharmacology Fast Forward. Published on October 16, 2017 as DOI: 10.1124/mol.117.109959 This article has not been copyedited and formatted. The final version may differ from this version. MOL #109959 Title: Activation of Human Transient Receptor Potential Melastatin-8 (TRPM8) by Calcium- Rich Particulate Materials and Effects on Human Lung Cells Authors: John G. Lamb, Erin G. Romero, Zhenyu Lu, Seychelle K. Marcus, Hannah C. Peterson, John M. Veranth, Cassandra E. Deering-Rice, and Christopher A. Reilly Affiliations: (J.G.L., E.G.R., Z.L., S.K.M., H.C.P., J.M.V., C.E.D-R., and C.A.R.) Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, 30 S. 2000 E., Room 201 Skaggs Hall, Salt Lake City, UT 84112, USA. Downloaded from molpharm.aspetjournals.org at ASPET Journals on September 27, 2021 1 Molecular Pharmacology Fast Forward. Published on October 16, 2017 as DOI: 10.1124/mol.117.109959 This article has not been copyedited and formatted. The final version may differ from this version. MOL #109959 Running Title: Activation of TRPM8 by Particles *Corresponding author: Dr. Christopher A. Reilly, Ph.D. University of Utah Department of Pharmacology and Toxicology 30 South 2000 East, 201 Skaggs Hall Salt Lake City, UT 84112 Phone: (801) 581-5236; FAX: (801) 585-5111 Email: [email protected] Number of text pages: 41 Downloaded from Number of Tables: 2 Number of Figures: 7 References: 40 Number of words in Abstract: 245 Number of words in Introduction: 704 molpharm.aspetjournals.org Number
  • (12) United States Patent (10) Patent No.: US 7,906,307 B2 S0e Et Al

    (12) United States Patent (10) Patent No.: US 7,906,307 B2 S0e Et Al

    US007906307B2 (12) United States Patent (10) Patent No.: US 7,906,307 B2 S0e et al. (45) Date of Patent: Mar. 15, 2011 (54) VARIANT LIPIDACYLTRANSFERASES AND 4,683.202 A 7, 1987 Mullis METHODS OF MAKING 4,689,297 A 8, 1987 Good 4,707,291 A 11, 1987 Thom 4,707,364 A 11/1987 Barach (75) Inventors: Jorn Borch Soe, Tilst (DK); Jorn 4,708,876 A 1 1/1987 Yokoyama Dalgaard Mikkelson, Hvidovre (DK); 4,798,793 A 1/1989 Eigtved 4,808,417 A 2f1989 Masuda Arno de Kreij. Geneve (CH) 4,810,414 A 3/1989 Huge-Jensen 4,814,331 A 3, 1989 Kerkenaar (73) Assignee: Danisco A/S, Copenhagen (DK) 4,818,695 A 4/1989 Eigtved 4,826,767 A 5/1989 Hansen 4,865,866 A 9, 1989 Moore (*) Notice: Subject to any disclaimer, the term of this 4,904.483. A 2f1990 Christensen patent is extended or adjusted under 35 4,916,064 A 4, 1990 Derez U.S.C. 154(b) by 0 days. 5,112,624 A 5/1992 Johna 5,213,968 A 5, 1993 Castle 5,219,733 A 6/1993 Myojo (21) Appl. No.: 11/852,274 5,219,744 A 6/1993 Kurashige 5,232,846 A 8, 1993 Takeda (22) Filed: Sep. 7, 2007 5,264,367 A 11/1993 Aalrust (Continued) (65) Prior Publication Data US 2008/OO70287 A1 Mar. 20, 2008 FOREIGN PATENT DOCUMENTS AR 331094 2, 1995 Related U.S. Application Data (Continued) (63) Continuation-in-part of application No.
  • Properties and Therapeutic Potential of Transient Receptor Potential Channels with Putative Roles in Adversity: Focus on TRPC5, TRPM2 and TRPA1

    Properties and Therapeutic Potential of Transient Receptor Potential Channels with Putative Roles in Adversity: Focus on TRPC5, TRPM2 and TRPA1

    724 Current Drug Targets, 2011, 12, 724-736 Properties and Therapeutic Potential of Transient Receptor Potential Channels with Putative Roles in Adversity: Focus on TRPC5, TRPM2 and TRPA1 L.H. Jiang, N. Gamper and D.J. Beech* Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK Abstract: Mammals contain 28 genes encoding Transient Receptor Potential (TRP) proteins. The proteins assemble into cationic channels, often with calcium permeability. Important roles in physiology and disease have emerged and so there is interest in whether the channels might be suitable therapeutic drug targets. Here we review selected members of three subfamilies of mammalian TRP channel (TRPC5, TRPM2 and TRPA1) that show relevance to sensing of adversity by cells and biological systems. Summarized are the cellular and tissue distributions, general properties, endogenous modulators, protein partners, cellular and tissue functions, therapeutic potential, and pharmacology. TRPC5 is stimulated by receptor agonists and other factors that include lipids and metal ions; it heteromultimerises with other TRPC proteins and is involved in cell movement and anxiety control. TRPM2 is activated by hydrogen peroxide; it is implicated in stress-related inflammatory, vascular and neurodegenerative conditions. TRPA1 is stimulated by a wide range of irritants including mustard oil and nicotine but also, controversially, noxious cold and mechanical pressure; it is implicated in pain and inflammatory responses, including in the airways. The channels have in common that they show polymodal stimulation, have activities that are enhanced by redox factors, are permeable to calcium, and are facilitated by elevations of intracellular calcium. Developing inhibitors of the channels could lead to new agents for a variety of conditions: for example, suppressing unwanted tissue remodeling, inflammation, pain and anxiety, and addressing problems relating to asthma and stroke.
  • Cannabinoid Ligands Targeting TRP Channels By

    Cannabinoid Ligands Targeting TRP Channels By

    Cannabinoid ligands targeting TRP channels By: Chanté Muller, Paula Morales, and Patricia H. Reggio Muller, C., Morales, P., & Reggio, P.H. (2019). Cannabinoid ligands targeting TRP channels. Frontiers in Molecular Neuroscience, 11, 497. https://doi.org/10.3389/fnmol.2018.00487 © 2019 Muller, Morales and Reggio. Published under a Creative Commons Attribution International License (CC BY 4.0); https://creativecommons.org/licenses/by/4.0/. Abstract: Transient receptor potential (TRP) channels are a group of membrane proteins involved in the transduction of a plethora of chemical and physical stimuli. These channels modulate ion entry, mediating a variety of neural signaling processes implicated in the sensation of temperature, pressure, and pH, as well as smell, taste, vision, and pain perception. Many diseases involve TRP channel dysfunction, including neuropathic pain, inflammation, and respiratory disorders. In the pursuit of new treatments for these disorders, it was discovered that cannabinoids can modulate a certain subset of TRP channels. The TRP vanilloid (TRPV), TRP ankyrin (TRPA), and TRP melastatin (TRPM) subfamilies were all found to contain channels that can be modulated by several endogenous, phytogenic, and synthetic cannabinoids. To date, six TRP channels from the three subfamilies mentioned above have been reported to mediate cannabinoid activity: TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8. The increasing data regarding cannabinoid interactions with these receptors has prompted some researchers to consider these TRP channels to be “ionotropic cannabinoid receptors.” Although CB1 and CB2 are considered to be the canonical cannabinoid receptors, there is significant overlap between cannabinoids and ligands of TRP receptors. The first endogenous agonist of TRPV1 to be discovered was the endocannabinoid, anandamide (AEA).
  • TRPV1: Structure, Endogenous Agonists, and Mechanisms

    TRPV1: Structure, Endogenous Agonists, and Mechanisms

    International Journal of Molecular Sciences Review TRPV1: Structure, Endogenous Agonists, and Mechanisms Miguel Benítez-Angeles, Sara Luz Morales-Lázaro, Emmanuel Juárez-González and Tamara Rosenbaum * Departamento de Neurociencia Cognitiva, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; [email protected] (M.B.-A.); [email protected] (S.L.M.-L.); [email protected] (E.J.-G.) * Correspondence: [email protected]; Tel.: +52-555-622-56-24; Fax: +52-555-622-56-07 Received: 1 April 2020; Accepted: 29 April 2020; Published: 12 May 2020 Abstract: The Transient Receptor Potential Vanilloid 1 (TRPV1) channel is a polymodal protein with functions widely linked to the generation of pain. Several agonists of exogenous and endogenous nature have been described for this ion channel. Nonetheless, detailed mechanisms and description of binding sites have been resolved only for a few endogenous agonists. This review focuses on summarizing discoveries made in this particular field of study and highlighting the fact that studying the molecular details of activation of the channel by different agonists can shed light on biophysical traits that had not been previously demonstrated. Keywords: TRP channels; TRPV1; pain; agonist; structure 1. Introduction Since the Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel was cloned in the last years of the 20th century [1], there have been extensive efforts to reveal the structural and functional details of this protein. Thus, nowadays it is one of the best characterized members of the TRP family of ion channels. TRPV1 is mainly expressed by trigeminal ganglion (TG) neurons and by small-diameter neurons within sensory ganglia such as the dorsal root ganglion (DRG).
  • SANTOS, GABRIELA TREVISAN DOS.Pdf (5.044Mb)

    SANTOS, GABRIELA TREVISAN DOS.Pdf (5.044Mb)

    UNIVERSIDADE FEDERAL DE SANTA MARIA CENTRO DE CIÊNCIAS NATURAIS E EXATAS PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS BIOLÓGICAS: BIOQUÍMICA TOXICOLÓGICA CARACTERIZAÇÃO DO ESTERÓIDE α-ESPINASTEROL COMO UM NOVO ANTAGONISTA DO RECEPTOR TRPV1 COM EFEITO ANTINOCICEPTIVO DISSERTAÇÃO DE MESTRADO Gabriela Trevisan dos Santos Santa Maria, RS, Brasil 2011 α CARACTERIZAÇÃO DO ESTERÓIDE -ESPINASTEROL COMO UM NOVO ANTAGONISTA DO RECEPTOR TRPV1 COM EFEITO ANTINOCICEPTIVO Por Gabriela Trevisan dos Santos Dissertação apresentada ao curso de Mestrado do Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica da Universidade Federal de Santa Maria (UFSM, RS), como requisito parcial para obtenção do grau de Mestre em Ciências Biológicas: Bioquímica Toxicológica. Orientador: Prof. Dr. Juliano Ferreira Santa Maria, RS, Brasil 2011 Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica A comissão examinadora, abaixo assinada, Aprova a Dissertação de Mestrado CARACTERIZAÇÃO DO ESTERÓIDE α-ESPINASTEROL COMO UM NOVO ANTAGONISTA DO RECEPTOR TRPV1 COM EFEITO ANTINOCICEPTIVO elaborada por Gabriela Trevisan dos Santos Como requisito parcial para obtenção do grau de Mestre em Ciências Biológicas: Bioquímica Toxicológica COMISSÃO EXAMINADORA ___________________________________ Juliano Ferreira, Dr. (Orientador) ________________________________ Maria Rosa Chitolina Schetinger, Dra. (UFSM) ___________________________________ Roselei Fachinetto, Dra. (UFSM) Santa Maria, 1 de Setembro de 2011 AGRADECIMENTOS Agradeço a Deus por iluminar meu caminho e me dar forças para seguir sempre em frente. Aos meus familiares, em especial, a meus pais Joaquim e Claudia, e ao meu irmão Guilherme, pelo apoio incondicional, o que contribuiu para que todos os momentos difíceis se tornassem passageiros. Ao meu orientador, Juliano Ferreira, pela oportunidade oferecida, pelos conselhos, ensinamentos e principalmente pelo bom convívio em todos estes anos de trabalho.