Tyramine and Amyloid Beta 42: a Toxic Synergy
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Neurotransmitter Resource Guide
NEUROTRANSMITTER RESOURCE GUIDE Science + Insight doctorsdata.com Doctor’s Data, Inc. Neurotransmitter RESOURCE GUIDE Table of Contents Sample Report Sample Report ........................................................................................................................................................................... 1 Analyte Considerations Phenylethylamine (B-phenylethylamine or PEA) ................................................................................................. 1 Tyrosine .......................................................................................................................................................................................... 3 Tyramine ........................................................................................................................................................................................4 Dopamine .....................................................................................................................................................................................6 3, 4-Dihydroxyphenylacetic Acid (DOPAC) ............................................................................................................... 7 3-Methoxytyramine (3-MT) ............................................................................................................................................... 9 Norepinephrine ........................................................................................................................................................................ -
Is TAAR1 a Potential Therapeutic Target for Immune Dysregulation In
Graduate Physical and Life Sciences PhD Pharmacology Abstract ID# 1081 Is TAAR1 a Potential Therapeutic Target for Immune Dysregulation in Drug Abuse? Fleischer, Lisa M; Tamashunas, Nina and Miller, Gregory M Addiction Sciences Laboratory, Northeastern University, Boston MA 02115 Abstract Discovered in 2001, Trace Amine Associated Receptor 1 (TAAR1) is a direct target of Data and Results amphetamine, methamphetamine and MDMA. It is expressed in the brain reward circuity and modulates dopamine transporter function and dopamine neuron firing rates. Newly-developed compounds that specifically target TAAR1 have recently been investigated in animal models In addition to brain, TAAR1 is expressed in immune cells METH promotes PKA and PKC Phosphorylation through TAAR1 as candidate therapeutics for methamphetamine, cocaine and alcohol abuse. These studies • We treated HEK/TAAR1 cells and HEK293 involving classic behavioral measures of drug response, as well as drug self-administration, Rhesus and Human cells with vehicle or METH, with and without strongly implicate TAAR1 as a potential therapeutic target for the treatment of addiction. In activators and inhibitors of PKA and PKC. addition to its central actions, we demonstrated that TAAR1 is upregulated in peripheral blood Cells Lines mononuclear cells (PBMC) and B cells following immune activation, and that subsequent • We performed Western blotting experiments to activation of TAAR1 by methamphetamine stimulates cAMP, similar to the function of measure levels of phospho-PKA and phospho- adenosine A2 receptors which are also present in immune cells and play a critical role in the PKC. immune response. Here, we are investigating the relationship between TAAR1 and the • We found that specific activators of PKA and adenosine A2 receptor at the level of cellular signaling and receptor dimerization. -
Emerging Evidence for a Central Epinephrine-Innervated A1- Adrenergic System That Regulates Behavioral Activation and Is Impaired in Depression
Neuropsychopharmacology (2003) 28, 1387–1399 & 2003 Nature Publishing Group All rights reserved 0893-133X/03 $25.00 www.neuropsychopharmacology.org Perspective Emerging Evidence for a Central Epinephrine-Innervated a1- Adrenergic System that Regulates Behavioral Activation and is Impaired in Depression ,1 1 1 1 1 Eric A Stone* , Yan Lin , Helen Rosengarten , H Kenneth Kramer and David Quartermain 1Departments of Psychiatry and Neurology, New York University School of Medicine, New York, NY, USA Currently, most basic and clinical research on depression is focused on either central serotonergic, noradrenergic, or dopaminergic neurotransmission as affected by various etiological and predisposing factors. Recent evidence suggests that there is another system that consists of a subset of brain a1B-adrenoceptors innervated primarily by brain epinephrine (EPI) that potentially modulates the above three monoamine systems in parallel and plays a critical role in depression. The present review covers the evidence for this system and includes findings that brain a -adrenoceptors are instrumental in behavioral activation, are located near the major monoamine cell groups 1 or target areas, receive EPI as their neurotransmitter, are impaired or inhibited in depressed patients or after stress in animal models, and a are restored by a number of antidepressants. This ‘EPI- 1 system’ may therefore represent a new target system for this disorder. Neuropsychopharmacology (2003) 28, 1387–1399, advance online publication, 18 June 2003; doi:10.1038/sj.npp.1300222 Keywords: a1-adrenoceptors; epinephrine; motor activity; depression; inactivity INTRODUCTION monoaminergic systems. This new system appears to be impaired during stress and depression and thus may Depressive illness is currently believed to result from represent a new target for this disorder. -
Mt-Atp8 Gene in the Conplastic Mouse Strain C57BL/6J-Mtfvb/NJ on the Mitochondrial Function and Consequent Alterations to Metabolic and Immunological Phenotypes
From the Lübeck Institute of Experimental Dermatology of the University of Lübeck Director: Prof. Dr. Saleh M. Ibrahim Interplay of mtDNA, metabolism and microbiota in the pathogenesis of AIBD Dissertation for Fulfillment of Requirements for the Doctoral Degree of the University of Lübeck from the Department of Natural Sciences Submitted by Paul Schilf from Rostock Lübeck, 2016 First referee: Prof. Dr. Saleh M. Ibrahim Second referee: Prof. Dr. Stephan Anemüller Chairman: Prof. Dr. Rainer Duden Date of oral examination: 30.03.2017 Approved for printing: Lübeck, 06.04.2017 Ich versichere, dass ich die Dissertation ohne fremde Hilfe angefertigt und keine anderen als die angegebenen Hilfsmittel verwendet habe. Weder vorher noch gleichzeitig habe ich andernorts einen Zulassungsantrag gestellt oder diese Dissertation vorgelegt. ABSTRACT Mitochondria are critical in the regulation of cellular metabolism and influence signaling processes and inflammatory responses. Mitochondrial DNA mutations and mitochondrial dysfunction are known to cause a wide range of pathological conditions and are associated with various immune diseases. The findings in this work describe the effect of a mutation in the mitochondrially encoded mt-Atp8 gene in the conplastic mouse strain C57BL/6J-mtFVB/NJ on the mitochondrial function and consequent alterations to metabolic and immunological phenotypes. This work provides insights into the mutation-induced cellular adaptations that influence the inflammatory milieu and shape pathological processes, in particular focusing on autoimmune bullous diseases, which have recently been reported to be associated with mtDNA polymorphisms in the human MT-ATP8 gene. The mt-Atp8 mutation diminishes the assembly of the ATP synthase complex into multimers and decreases mitochondrial respiration, affects generation of reactive oxygen species thus leading to a shift in the metabolic balance and reduction in the energy state of the cell as indicated by the ratio ATP to ADP. -
Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REPORT Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ Ortal Barel,1 Zamir Shorer,2 Hagit Flusser,2 Rivka Ofir,1 Ginat Narkis,1 Gal Finer,1 Hanah Shalev,2 Ahmad Nasasra,2 Ann Saada,3 and Ohad S. Birk1,4,* A consanguineous Israeli Bedouin kindred presented with an autosomal-recessive nonlethal phenotype of severe psychomotor retarda- tion and extrapyramidal signs, dystonia, athetosis and ataxia, mild axial hypotonia, and marked global dementia with defects in verbal and expressive communication skills. Metabolic workup was normal except for mildly elevated blood lactate levels. Brain magnetic resonance imaging (MRI) showed increased density in the putamen, with decreased density and size of the caudate and lentiform nuclei. Reduced activity specifically of mitochondrial complex III and variable decrease in complex I activity were evident in muscle biopsies. Homozygosity of affected individuals to UQCRB and to BCSIL, previously associated with isolated complex III deficiency, was ruled out. Genome-wide linkage analysis identified a homozygosity locus of approximately 9 cM on chromosome 5q31 that was further narrowed down to 2.14 cM, harboring 30 genes (logarithm of the odds [LOD] score 8.82 at q ¼ 0). All 30 genes were sequenced, revealing a single missense (p.Ser45Phe) mutation in UQCRQ (encoding ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5 kDa), one of the ten nuclear -
Neurotransmitters-Drugs Andbrain Function.Pdf
Neurotransmitters, Drugs and Brain Function. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 Neurotransmitters, Drugs and Brain Function Neurotransmitters, Drugs and Brain Function. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 Neurotransmitters, Drugs and Brain Function Edited by R. A. Webster Department of Pharmacology, University College London, UK JOHN WILEY & SONS, LTD Chichester Á New York Á Weinheim Á Brisbane Á Singapore Á Toronto Neurotransmitters, Drugs and Brain Function. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 Copyright # 2001 by John Wiley & Sons Ltd. Bans Lane, Chichester, West Sussex PO19 1UD, UK National 01243 779777 International ++44) 1243 779777 e-mail +for orders and customer service enquiries): [email protected] Visit our Home Page on: http://www.wiley.co.uk or http://www.wiley.com All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London W1P0LP,UK, without the permission in writing of the publisher. Other Wiley Editorial Oces John Wiley & Sons, Inc., 605 Third Avenue, New York, NY 10158-0012, USA WILEY-VCH Verlag GmbH, Pappelallee 3, D-69469 Weinheim, Germany John Wiley & Sons Australia, Ltd. -
2-Phenylethylamine and Methamphetamine Enhance the Spinal Monosynaptic Reflex by Releasing Noradrenaline from the Terminals of Descending Fibers
Japan. J. Pharmacol. 55, 359-366 (1991) 359 2-Phenylethylamine and Methamphetamine Enhance the Spinal Monosynaptic Reflex by Releasing Noradrenaline from the Terminals of Descending Fibers Hideki Ono, Hiroyuki Ito and Hideomi Fukuda' Departmentof Toxicologyand Pharmacology,Faculty of Pharmaceutical Sciences, TheUniversity of Tokyo,Hongo 7-3-1, Bunkyo-ku, Tokyo 113, Japan 'Departmentof Pharmacology, Collegeof Pharmacy,Nihon University, 7-7-1Narashinodai, Funabashi, Chiba 274, Japan ReceivedJuly 28, 1990 AcceptedDecember 27, 1990 ABSTRACT Experiments were performed on spinalized rats transected at C1. In travenous administration of 2-phenylethylamine-HC1 (PEA-HC1) (0.3 and 1 mg/kg, i.v.) and methamphetamine-HC1 (MAP-HC1) (0.1 and 0.3 mg/kg, i.v.) increased the amplitude of the monosynaptic reflex (MSR). The increase of the MSR caused by PEA and MAP was antagonized by prazosin-HC1 and abolished by the pretreatment with reserpine (i.p.) and 6-hydroxydopamine (intracisternally, 14 days previously). A dopamine D, antagonist, SK&F 83566-HBr (0.01 mg/kg, i.v. ), and a D2 antagonist, YM-09151-2 (0.3 mg/kg, i.v.), did not antagonize the increasing effects produced by PEA and MAP. An inhibitor of type-B monoamine oxidase, (-)deprenyl-HC1 (1 mg/kg, i.v.), prolonged the effect of PEA but not that of MAP, suggesting that PEA alone, and not its metabolites, enhanced the MSR. These results suggest that PEA and MAP increase the amplitude of the MSR by releasing noradrenaline from the ter minals of descending noradrenergic fibers, and that PEA, an endogenous trace amine, has a mechanism of action similar to that of MAP. -
Effects of the Trace Amine Associated Receptor 1 Agonist RO5263397 On
International Journal of Neuropsychopharmacology, 2015, 1–7 doi:10.1093/ijnp/pyu060 Research Article research article Effects of the Trace Amine Associated Receptor 1 Agonist RO5263397 on Abuse-Related Behavioral Indices of Methamphetamine in Rats Li Jing, PhD; Yanan Zhang, PhD; Jun-Xu Li, PhD Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY (Drs Jing and Li); Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China (Dr Jing); Research Triangle Institute, Research Triangle Park, NC (Dr Zhang). Correspondence: Jun-Xu Li, PhD, Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY ([email protected]). Abstract Background: Methamphetamine is a major drug of abuse with no effective pharmacotherapy available. Trace amine associated receptor 1 is implicated in cocaine addiction and represents a potential therapeutic target. However, the effects of trace amine associated receptor 1 agonists on addiction-related behavioral effects of methamphetamine are unknown. Methods: This study examined the effects of a trace amine associated receptor 1 agonist RO5263397 on methamphetamine- induced behavioral sensitization, methamphetamine self-administration, cue- and methamphetamine-induced reinstatement of drug seeking, and cue-induced reinstatement of sucrose-seeking behaviors in rats. Male Sprague-Dawley rats were used to examine the effects of methamphetamine alone and in combination with the trace amine associated receptor 1 agonist RO5263397 (3.2–10 mg/kg). Results: RO5263397 dose-dependently attenuated the expression of behavioral sensitization to methamphetamine, reduced methamphetamine self-administration, and decreased both cue- and a priming dose of methamphetamine-induced reinstatement of drug-seeking behaviors. -
Biomarkers of Mitotoxicity After Acute Liver Injury: Further Insights Into the Interpretation of Glutamate Dehydrogenase
Journal of Clinical and Translational Research 10.18053/Jctres/07.202101.005 MINI REVIEW Biomarkers of mitotoxicity after acute liver injury: further insights into the interpretation of glutamate dehydrogenase Mitchell R. McGill1,2* and Hartmut Jaeschke3 1. Department of Environmental Health Sciences, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, 4301 W. Markham St, Little Rock, AR, USA, 72205 2. Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR, USA, 72205 3. Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, USA, 66160 *Corresponding author Mitchell R. McGill, PhD Department of Environmental Health Sciences & Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR Tel: +1 501-526-6696 Email: [email protected] Article information: Received: November 03, 2020 Revised: December 09, 2020 Accepted: December 10, 2020 Journal of Clinical and Translational Research 10.18053/Jctres/07.202101.005 ABSTRACT Background: Acetaminophen (APAP) is a popular analgesic, but overdose causes acute liver injury and sometimes death. Decades of research have revealed that mitochondrial damage is central in the mechanisms of toxicity in rodents, but we know much less about the role of mitochondria in humans. Due to the challenge of procuring liver tissue from APAP overdose patients, non-invasive mechanistic biomarkers are necessary to translate the mechanisms of APAP hepatotoxicity from rodents to patients. It was recently proposed that the mitochondrial matrix enzyme glutamate dehydrogenase (GLDH) can be measured in circulation as a biomarker of mitochondrial damage. -
Selegiline) in Monkeys*
Intravenous self-administration studies with /-deprenyl (selegiline) in monkeys* /-Deprenyl and its stereoisomer d-deprenyl did not maintain intravenous self-administration behavior in rhesus monkeys. In contrast, /-methamphetamine, the major metabolite of /-deprenyl, as well as the baseline drug, cocaine, maintained high rates of intravenous self-administration behavior. Treatment with /-deprenyl doses up to 1.0 mg/kg before self-administration sessions failed to alter self-administra- tion of either cocaine or /-methamphetamine. Thus /-deprenyl did not appear to have cocaine- or meth- amphetamine-like reinforcing properties in monkeys and was ineffective in altering established patterns of psychomotor-stimulant self-administration behavior. These results support clinical findings that de- spite long-term use of /-deprenyl for the treatment of Parkinson's disease by large numbers of patients, no instances of abuse have been documented. /-Deprenyl has recently been suggested as a potential med- ication for the treatment of various types of drug abuse, including cocaine abuse, but its failure to pro- duce selective effects in decreasing cocaine or methamphetamine self-administration behavior in the present experiments makes such an application seem unlikely. (CLIN PHARMACOL THER 1994;56:774-80.) Gail D. Winger, PhD,a Sevil Yasar, MD,b'd'e S. Steven Negus, PhD,a and Steven R. Goldberg, pIli/i d'e Ann Arbor, Mich., and Baltimore, Md. From the 'Department of Pharmacology, University of Michigan /-Deprenyl (selegiline) has been known for several -
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Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord Elizabeth A. Gozal, Emory University Brannan E. O'Neill, Emory University Michael A. Sawchuk, Emory University Hong Zhu, Emory University Mallika Halder, Emory University Chou Ching-Chieh , Emory University Shawn Hochman, Emory University Journal Title: Frontiers in Neural Circuits Volume: Volume 8 Publisher: Frontiers | 2014-11-07, Pages 134-134 Type of Work: Article | Final Publisher PDF Publisher DOI: 10.3389/fncir.2014.00134 Permanent URL: https://pid.emory.edu/ark:/25593/mr95r Final published version: http://dx.doi.org/10.3389/fncir.2014.00134 Copyright information: © 2014 Gozal, O'Neill, Sawchuk, Zhu, Halder, Chou and Hochman. This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits distribution of derivative works, making multiple copies, distribution, public display, and publicly performance, provided the original work is properly cited. This license requires credit be given to copyright holder and/or author, copyright and license notices be kept intact. Accessed September 27, 2021 11:18 AM EDT ORIGINAL RESEARCH ARTICLE published: 07 November 2014 NEURAL CIRCUITS doi: 10.3389/fncir.2014.00134 Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord Elizabeth A. Gozal , Brannan E. O’Neill , Michael A. Sawchuk , Hong Zhu , Mallika Halder , Ching-Chieh Chou and Shawn Hochman* Physiology Department, Emory University, Atlanta, GA, USA Edited by: The trace amines (TAs), tryptamine, tyramine, and β-phenylethylamine, are synthesized Brian R. -
Food Sources and Biomolecular Targets of Tyramine
Special Article Food sources and biomolecular targets of tyramine Gaby Andersen, Patrick Marcinek, Nicole Sulzinger, Peter Schieberle, and Dietmar Krautwurst Tyramine is a biogenic trace amine that is generated via the decarboxylation of the amino acid tyrosine. At pico- to nanomolar concentrations, it can influence a multi- tude of physiological mechanisms, exhibiting neuromodulatory properties as well as cardiovascular and immunological effects. In humans, the diet is the primary Downloaded from https://academic.oup.com/nutritionreviews/article/77/2/107/5084469 by guest on 24 September 2021 source of physiologically relevant tyramine concentrations, which are influenced by a large number of intrinsic and extrinsic factors. Among these factors are the avail- ability of tyrosine in food, the presence of tyramine-producing bacteria, the environ- mental pH, and the salt content of food. The process of fermentation provides a particularly good source of tyramine in human nutrition. Here, the potential impact of dietary tyramine on human health was assessed by compiling quantitative data on the tyramine content in a variety of foods and then conducting a brief review of the literature on the physiological, cellular, and systemic effects of tyramine. Together, the data sets presented here may allow both the assessment of tyramine concentrations in food and the extrapolation of these concentrations to gauge the physiological and systemic effects in the context of human nutrition. INTRODUCTION presence of tyramine in a variety of foods, (2) the post- prandial physiological and adverse effects of tyramine, Tyramine is a biogenic amine generated via the decar- and (3) the biomolecular targets of tyramine. It is not boxylation of the amino acid tyrosine in animals, plants, intended to be a systematic or comprehensive review of and microorganisms.