Anti-ALOX15 Monoclonal Antibody, Clone 4H9 (DCABH-1151) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use

Total Page：16

File Type：pdf, Size：1020Kb

Anti-ALOX15 monoclonal antibody, clone 4H9 (DCABH-1151) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Product Overview Mouse monoclonal to 15 Lipoxygenase 1 Antigen Description Converts arachidonic acid to 15S-hydroperoxyeicosatetraenoic acid. Also acts on C-12 of arachidonate as well as on linoleic acid. Immunogen Recombinant full length, Human 15 Lipoxygenase 1 produced in HEK293T cells (NP_001131). Isotype IgG2b Source/Host Mouse Species Reactivity Rat, Dog, Human, Monkey Clone 4H9 Purity Protein A purified Purification Purified from Mouse ascites fluids by affinity chromatography Conjugate Unconjugated Applications WB, IHC-P, ICC/IF Positive Control HEK293T cells transfected with pCMV6-ENTRY 15 Lipoxygenase 1 cDNA; HepG2, HeLa, A549, COS7, MDCK, PC12 and MCF7 cell extracts; Human breast, Human pancreas carcinoma, Human thyroid carcinoma, Human endometrium, Human endometrium adenocarcinoma, Human pros Format Liquid Size 100 μl Buffer pH: 7.30; Preservative: 0.02% Sodium azide; Constituents: 48% PBS, 50% Glycerol, 1% BSA Preservative 0.02% Sodium Azide Storage store at -20°C. Avoid repeated freeze / thaw cycles. Ship Shipped at 4°C. 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved GENE INFORMATION Gene Name ALOX15 arachidonate 15-lipoxygenase [ Homo sapiens ] Official Symbol ALOX15 Synonyms ALOX15; arachidonate 15-lipoxygenase; 15 LOX 1; 15-LOX; 15-lipooxygenase-1; arachidonate omega-6 lipoxygenase; 15LOX-1; 15-LOX-1; Entrez Gene ID 246 Protein Refseq NP_001131 UniProt ID P16050 Chromosome Location 17p13.3 Pathway Arachidonic acid metabolism, organism-specific biosystem; Arachidonic acid metabolism, conserved biosystem; Eicosanoid Synthesis, organism-specific biosystem; IL4-mediated signaling events, organism-specific biosystem; Linoleic acid metabolism, organism-specific biosystem; Linoleic acid metabolism, conserved biosystem; Metabolic pathways, organism- specific biosystem; Function arachidonate 12-lipoxygenase activity; arachidonate 15-lipoxygenase activity; hepoxilin-epoxide hydrolase activity; iron ion binding; lipoxygenase activity; metal ion binding; oxidoreductase activity; 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 2 © Creative Diagnostics All Rights Reserved.

Copy Link

Recommended publications

Open Thesis Master Document V5.0.Pdf
The Pennsylvania State University The Graduate School Department of Veterinary and Biomedical Science IDENTIFICATION OF ENDOGENOUS MODULATORS FOR THE ARYL HYDROCARBON RECEPTOR A Thesis in Genetics by Christopher R. Chiaro © 2007 Christopher R. Chiaro Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December, 2007 The thesis of Christopher R. Chiaro was reviewed and approved* by the following: Gary H. Perdew John T. and Paige S. Smith Professor in Agricultural Sciences Thesis Advisor Chair of Committee C. Channa Reddy Distinguished Professor of Veterinary Science A. Daniel Jones Senior Scientist Department of Chemistry John P. Vanden Heuvel Professor of Veterinary Science Richard Ordway Associate Professor of Biology Chair of Genetics Graduate Program *Signatures are on file in the Graduate School iii ABSTRACT The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor capable of being regulated by a structurally diverse array of chemicals ranging from environmental carcinogens to dietary metabolites. A member of the basic helix-loop- helix/ Per-Arnt-Sim (bHLH-PAS) super-family of DNA binding regulatory proteins, the AhR is an important developmental regulator that can be detected in nearly all mammalian tissues. Prior to ligand activation, the AhR resides in the cytosol as part of an inactive oligomeric protein complex comprised of the AhR ligand-binding subunit, a dimer of the 90 kDa heat shock protein, and a single molecule each of the immunophilin like X-associated protein 2 (XAP2) and p23 proteins. Functioning as chemosensor, the AhR responds to both endobiotic and xenobiotic derived chemical ligands by ultimately directing the expression of metabolically important target genes.
[Show full text]
Regulation of Tissue Inflammation by 12-Lipoxygenases
biomolecules Review Regulation of Tissue Inflammation by 12-Lipoxygenases Abhishek Kulkarni 1 , Jerry L. Nadler 2, Raghavendra G. Mirmira 1,* and Isabel Casimiro 1,* 1 Department of Medicine, The University of Chicago, Chicago, IL 60637, USA; [email protected] 2 Department of Medicine and Pharmacology, New York Medical College, Valhalla, NY 10595, USA; [email protected] * Correspondence: [email protected] (R.G.M.); [email protected] (I.C.) Abstract: Lipoxygenases (LOXs) are lipid metabolizing enzymes that catalyze the di-oxygenation of polyunsaturated fatty acids to generate active eicosanoid products. 12-lipoxygenases (12-LOXs) primarily oxygenate the 12th carbon of its substrates. Many studies have demonstrated that 12-LOXs and their eicosanoid metabolite 12-hydroxyeicosatetraenoate (12-HETE), have significant pathological implications in inflammatory diseases. Increased level of 12-LOX activity promotes stress (both oxidative and endoplasmic reticulum)-mediated inflammation, leading to damage in these tissues. 12-LOXs are also associated with enhanced cellular migration of immune cells—a characteristic of several metabolic and autoimmune disorders. Genetic depletion or pharmacological inhibition of the enzyme in animal models of various diseases has shown to be protective against disease development and/or progression in animal models in the setting of diabetes, pulmonary, cardiovascular, and metabolic disease, suggesting a translational potential of targeting the enzyme for the treatment of several disorders. In this article, we review the role of 12-LOXs in the pathogenesis of several diseases in which chronic inflammation plays an underlying role. Citation: Kulkarni, A.; Nadler, J.L.; Keywords: 12-lipoxygenases; 12-LOXs; 12/15-lipoxygenase; 12/15-LOX; lipoxygenases; eicosanoids; Mirmira, R.G.; Casimiro, I.
[Show full text]
Fatty Acid Metabolism Mediated by 12/15-Lipoxygenase Is a Novel Regulator of Hematopoietic Stem Cell Function and Myelopoiesis
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Spring 2010 Fatty Acid Metabolism Mediated by 12/15-Lipoxygenase is a Novel Regulator of Hematopoietic Stem Cell Function and Myelopoiesis Michelle Kinder University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Immunology and Infectious Disease Commons Recommended Citation Kinder, Michelle, "Fatty Acid Metabolism Mediated by 12/15-Lipoxygenase is a Novel Regulator of Hematopoietic Stem Cell Function and Myelopoiesis" (2010). Publicly Accessible Penn Dissertations. 88. https://repository.upenn.edu/edissertations/88 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/88 For more information, please contact [email protected]. Fatty Acid Metabolism Mediated by 12/15-Lipoxygenase is a Novel Regulator of Hematopoietic Stem Cell Function and Myelopoiesis Abstract Fatty acid metabolism governs critical cellular processes in multiple cell types. The goal of my dissertation was to investigate the intersection between fatty acid metabolism and hematopoiesis. Although fatty acid metabolism has been extensively studied in mature hematopoietic subsets during inflammation, in developing hematopoietic cells the role of fatty acid metabolism, in particular by 12/ 15-Lipoxygenase (12/15-LOX), was unknown. The observation that 12/15-LOX-deficient (Alox15) mice developed a myeloid leukemia instigated my studies since leukemias are often a consequence of dysregulated hematopoiesis. This observation lead to the central hypothesis of this dissertation which is that polyunsaturated fatty acid metabolism mediated by 12/15-LOX participates in hematopoietic development. Using genetic mouse models and in vitro and in vivo cell development assays, I found that 12/15-LOX indeed regulates multiple stages of hematopoiesis including the function of hematopoietic stem cells (HSC) and the differentiation of B cells, T cells, basophils, granulocytes and monocytes.
[Show full text]
Lipoxygenase Metabolites of Arachidonic Acid in Neuronal
TiPS - September 1990 [Vol. 11] 367 28 Takeda, N. et aL (1986) Acta Otolaryngol. Venerol. (Suppl. 115), 1-43 34 Pipkom, U. et al. (1987) Allergy 101,416-421 32 Granerus, G., Olafsson, I. H. and (Copenhagen) 42, 496-501 29 Tung, A. S. et al. (1985) Biochem. Roupe, G. (1985) Agents Actions 16, Pharmacol. 34, 3509-3515 244-248 30 August, T. F. el al. (1985) J. Pharm. Sci. 33 Neitaanmaki, H., Fraki, ]. E., Harvima, IPDllS1T: dimethyl-2-[4-(3-ethoxy-2- 74, 871-875 R. J. and Forstrom, L. (1989) Arch. hydroxypropoxy)phenylcarbamoyllethyl 31 Olafsson, I. H. (I985) Acta Derm. Dermatol. Res. 281, 99-104 sulfonium-p-toluene sulfonate polyacrylamide gel electrophor- Lipoxygenase metabolites of esis) and has no apparent cofactor requirement 4. A cDNA encoding arachidonic acid in neuronal leukocyte 12-1ipoxygenase has been isolated and sequenced 5. Like all other lipoxygenases, 12- transmembrane signalling lipoxygenase catalyses the intro- duction of molecular oxygen into Daniele Piomelli and Paul Greengard a 1,4-(cis,cis)-pentadiene moiety, converting arachidonic acid into the hydroperoxide, (12s)-hydro- Studies of invertebrate and vertebrate nervous tissue have demonstrated that peroxyeicosatetraenoic acid (12- free arachidonic acid and its lipoxygenase metabolites are produced in a HPETE) - a reaction that is both receptor-dependent fashion. The intracellular actions of these compounds regiospecific and stereospecific. include the regulation of activity of membrane ion channels and protein Other cis-polyunsaturated fatty kinases. In this article Daniele Piomelli and Paul Greengard review the acids, such as linoleic acid, lino- evidence that these lipophilic molecules constitute a novel class of intracellular lenic acid and docosahexaenoic second messenger, possibly involved in the modulation of neurotransmitter acid are also good substrates for release.
[Show full text]
Lipoxygenase-Generated Icosanoids Inhibit Glucose-Induced Insulin Release from Rat Islets
RostagiamJins Leukotrienes and Essential Fatty Acids (1990) 40.214 @ Longman Group UK Ltd 1990 Lipoxygenase-Generated Icosanoids Inhibit Glucose-induced Insulin Release from Rat Islets M. H. Nathan* and S. Belbez Pekt *Department of Internal Medicine (Division of Endocrinology and Metabolism), University of Michigan, Ann Arbor, Michigan, USA and ‘5560 Medical Sciences Research Building-2, University of Michigan Medical Center, Ann Arbor, MI 48109-0678, USA (Correspondence to SBP) ABSTRACT. Lipoxygenase-pathway metabolites of arachidonic acid are produced in pancreatic islets. They are are implicated in insulin release, since nonselective inhibitors of lipoxygenases inhibit glucose-induced insulin release. We studied the interplay in insulin release between glucose and selected icosanoids formed in 5-, 12- and 15-lipoxygenase pathways. Effects on immunoreactive insulin release of 10’ to 1O-6 12-(R)-HETE, 12-(S)-HETE, hepoxilin As, lipoxin Bq, LTB4 or LTC4 were tested individually in 30-min incubations of freshly isolated young adult Wistar rat pancreatic islets, in the presence of 5.6 mM or 23 mM glucose. Basal insulin release (at 5.6 mM glucose) was stimulated by LTC4 and hepoxilin A3 (304% and 234% of controls at 5.6 mM glucose alone, respectively), inhibited by 12-(S)-HPETE (56%), and was not affected by 12-(R)-HETE, 12-(S)-HETE, lipoxin B4 or LTB4 (ill%, 105%, 106% and 136%, respectively). Insulin release evoked by 23 mM glucose (190-320%) was inhibited (50-145%) by all icosanoids tested, except LTC4 (162%). We conclude that, among the lipoxygenase products tested, only leukotrienes and hepoxilin are candidates for a tonic-stimulatory influence on basal insulin release.
[Show full text]
Metabolism Pathways of Arachidonic Acids: Mechanisms and Potential Therapeutic Targets
Signal Transduction and Targeted Therapy www.nature.com/sigtrans REVIEW ARTICLE OPEN Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets Bei Wang1,2,3, Lujin Wu1,2, Jing Chen1,2, Lingli Dong3, Chen Chen 1,2, Zheng Wen1,2, Jiong Hu4, Ingrid Fleming4 and Dao Wen Wang1,2 The arachidonic acid (AA) pathway plays a key role in cardiovascular biology, carcinogenesis, and many inflammatory diseases, such as asthma, arthritis, etc. Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is in turn further metabolized by cyclooxygenases (COXs) and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes to a spectrum of bioactive mediators that includes prostanoids, leukotrienes (LTs), epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid (diHETEs), eicosatetraenoic acids (ETEs), and lipoxins (LXs). Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases (CVD), cancers, and inflammatory diseases. This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2. Thus, we herein present a synopsis of AA metabolism in human health, cardiovascular and cancer biology, and the signaling pathways involved in these processes. To explore the role of the AA metabolism and potential therapies, we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.
[Show full text]
3 Requires the Eicosanoid Hepoxilin a Pseudomonas Aeruginosa
Polymorphonuclear Cell Transmigration Induced by Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A 3 This information is current as Bryan P. Hurley, Dario Siccardi, Randall J. Mrsny and Beth of September 24, 2021. A. McCormick J Immunol 2004; 173:5712-5720; ; doi: 10.4049/jimmunol.173.9.5712 http://www.jimmunol.org/content/173/9/5712 Downloaded from References This article cites 40 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/173/9/5712.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Polymorphonuclear Cell Transmigration Induced by 1 Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A3 Bryan P. Hurley,*† Dario Siccardi,*†‡ Randall J. Mrsny,† and Beth A. McCormick2*† Lung inflammation resulting from bacterial infection of the respiratory mucosal surface in diseases such as cystic fibrosis and pneumonia contributes significantly to the pathology.
[Show full text]
Oxidation of Polyunsaturated Fatty Acids to Produce Lipid Mediators
Essays in Biochemistry (2020) 64 401–421 https://doi.org/10.1042/EBC20190082 Review Article Oxidation of polyunsaturated fatty acids to produce lipid mediators William W. Christie1 and John L. Harwood2 1James Hutton Institute, Invergowrie, Dundee, Scotland DD2 5DA, U.K.; 2School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, U.K. Correspondence: John L. Harwood ([email protected]) Downloaded from http://portlandpress.com/essaysbiochem/article-pdf/64/3/401/893636/ebc-2019-0082c.pdf by guest on 29 September 2021 The chemistry, biochemistry, pharmacology and molecular biology of oxylipins (defined as a family of oxygenated natural products that are formed from unsaturated fatty acids by pathways involving at least one step of dioxygen-dependent oxidation) are complex and occasionally contradictory subjects that continue to develop at an extraordinarily rapid rate. The term includes docosanoids (e.g. protectins, resolvins and maresins, or special- ized pro-resolving mediators), eicosanoids and octadecanoids and plant oxylipins, which are derived from either the omega-6 (n-6) or the omega-3 (n-3) families of polyunsaturated fatty acids. For example, the term eicosanoid is used to embrace those biologically active lipid mediators that are derived from C20 fatty acids, and include prostaglandins, thrombox- anes, leukotrienes, hydroxyeicosatetraenoic acids and related oxygenated derivatives. The key enzymes for the production of prostanoids are prostaglandin endoperoxide H synthases (cyclo-oxygenases), while lipoxygenases and oxidases of the cytochrome P450 family pro- duce numerous other metabolites. In plants, the lipoxygenase pathway from C18 polyunsat- urated fatty acids yields a variety of important products, especially the jasmonates, which have some comparable structural features and functions.
[Show full text]
Emerging Perspectives on Pain Management by Modulation of TRP Channels and ANO1
International Journal of Molecular Sciences Review Emerging Perspectives on Pain Management by Modulation of TRP Channels and ANO1 1, , 2, , 3, , 2, , Yasunori Takayama * y, Sandra Derouiche * y, Kenta Maruyama * y and Makoto Tominaga * y 1 Department of Physiology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan 2 Thermal Biology group, Exploratory Research Center on Life and Living Systems, National Institutes for Natural Sciences, 5-1 Aza-higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan 3 National Institute for Physiological Sciences, National Institutes for Natural Sciences, 5-1 Aza-higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan * Correspondence: [email protected] (Y.T.); [email protected] (S.D.); [email protected] (K.M.); [email protected] (M.T.) These authors contributed equally. y Received: 28 May 2019; Accepted: 9 July 2019; Published: 11 July 2019 Abstract: Receptor-type ion channels are critical for detection of noxious stimuli in primary sensory neurons. Transient receptor potential (TRP) channels mediate pain sensations and promote a variety of neuronal signals that elicit secondary neural functions (such as calcitonin gene-related peptide [CGRP] secretion), which are important for physiological functions throughout the body. In this review, we focus on the involvement of TRP channels in sensing acute pain, inﬂammatory pain, headache, migraine, pain due to fungal infections, and osteo-inﬂammation. Furthermore, action potentials mediated via interactions between TRP channels and the chloride channel, anoctamin 1 (ANO1), can also generate strong pain sensations in primary sensory neurons. Thus, we also discuss mechanisms that enhance neuronal excitation and are dependent on ANO1, and consider modulation of pain sensation from the perspective of both cation and anion dynamics.
[Show full text]
Hepoxilin B3 and Its Enzymatically Formed Derivative Trioxilin B3 Are Incorporated Into Phospholipids in Psoriatic Lesions
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions Rosa AntoÂn, Mercedes Camacho, LuõÂs Puig, and LuõÂs Vila Laboratory of In¯ammation Mediators, Institute of Research of the Santa Creu i Sant Pau Hospital, Barcelona, Spain In previous studies we observed that normal human position of glycerophospholipids. The thin layer epidermis forms 12-oxo-eicosatetraenoic acid (12- chromatography analysis of the phospholipid classes 14 oxo-ETE) and hepoxilin B3 (HxB3) as major eicosa- after incubation of epidermal cells with [ C]-labeled noids, both being elevated in psoriasis. We also HxB3, TrXB3, 12-hydroxy-eicosatetraenoic acid (12- observed that normal epidermis, in a reaction prob- HETE), 12-oxo-ETE, or 15-HETE showed that 12- ably catalyzed by 12-lipoxygenase, only synthesize HETE was the most esteri®ed (12-HETE > 15-HETE one of the two possible 10-hydroxy epimers of > TrXB3 > 12-oxo-ETE > HxB3). HxB3 and TrXB3 HxB3. We have now extended these previous studies were mainly esteri®ed in phosphatidyl-choline and investigating further transformation of HxB3 into phosphatidyl-ethanolamine. HxB3 was also enzyma- trioxilin B3 (TrXB3) and esteri®cation of both into tically converted into TrXB3 in vitro. HxB3 epoxide phospholipids. Phospholipids were extracted from hydrolase-like activity was not observed when boiled 14 normal epidermis and from psoriatic scales. A com- tissue was incubated with [ C]-HxB3, this activity bination of high performance liquid chromatography being located in the cytosol fraction (100,000 3 g and gas chromatography±mass spectrometry analysis supernatant) of fresh tissue.
[Show full text]
Schneider, C., Schwab, W., Humpf, H.-U., and Schreier, P
Curriculum Vitae Name: Dr. Claus Schneider Office Address: 514A RRB Office Phone: 615-343-9539 Email: [email protected] Date and Place of Birth: 27 December 1966 in Karlstadt, Germany Citizenship: German and U.S. Personal data Home Address: 1102 Riverside Rd. Old Hickory, TN 37138, U.S.A. Home Phone: 615-847-2316 Education 09/77 – 05/86 High school Johann-Schöner-Gymnasium, Karlstadt, Germany 03/87 – 10/88 Community service (alternative military service) 10/88 – 12/92 College Universität Würzburg, Germany (Food Chemistry; 1. Staatsexamen) 04/94 – 07/96 Universität Würzburg, Germany (Philosophy, Linguistics, and Political Sciences) 01/93 – 10/96 Graduate School (Dissertation) Department of Food Chemistry, Universität Würzburg, Germany Supervisor: Prof. Dr. Peter Schreier; Title: “Über den Metabolismus von Fettsäurehydroperoxiden in Pflanzen: Untersuchungen zu Substraten und Produkten der Allenoxidsynthase (EC 4.2.1.92) aus Leinsamen (Linum usitatissimum L.)” 05/97 Degree: Ph.D. (Dr. rer. nat.) 01/97 – 07/97 Internship Landesuntersuchungsamt für das Gesundheitswesen Nordbayern, Erlangen, Germany (State food control laboratory) 08/97 Degree: Staatlich geprüfter Lebensmittelchemiker (2. Staatsexamen) 02/98 – 06/01 Postgraduate Training Department of Pharmacology, Vanderbilt University Medical School, Nashville, TN. Mentor: Alan R. Brash, Ph.D. Academic Appointments 10/13 – present Associate Professor Department of Pharmacology, Vanderbilt University Medical School 11/06 – 09/13 Assistant Professor Department of Pharmacology,
[Show full text]
NIH Public Access Author Manuscript Nat Neurosci
NIH Public Access Author Manuscript Nat Neurosci. Author manuscript; available in PMC 2015 February 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Nat Neurosci. 2014 February ; 17(2): 164–174. doi:10.1038/nn.3612. Peripheral gating of pain signals by endogenous analgesic lipids Daniele Piomelli1,2 and Oscar Sasso2 1Departments of Anatomy and Neurobiology, Pharmacology and Biological Chemistry, University of California, Irvine, USA 92697 2Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy 16163 Abstract Primary sensory afferents and their neighboring host-defense cells are a rich source of lipid- derived mediators that contribute to the sensation of pain caused by tissue damage and inflammation. But an increasing number of lipid molecules have been shown to act in an opposite way, to suppress the inflammatory process, restore homeostasis in damaged tissues and attenuate pain sensitivity by regulating neural pathways that transmit nociceptive signals from the periphery of the body to the central nervous system. The ‘gate control theory’ of pain postulates that neural circuits in the central nervous system (CNS) dynamically regulate nociceptive signals arising in the periphery of the body. Since its formulation in 19651, this theory has provided a framework in which to interpret the actions of central analgesic circuits, such as those recruited during acute stress or placebo responses. Emerging evidence indicates, however, that nociceptive signals may be subject to a dynamic filtering process even before they reach the spinal cord. Primary sensory neurons and the host-defense cells surrounding them release a variety of analgesic factors that control the traffic of nociceptive information to the CNS (Figure 1).
[Show full text]