The Effects of Adenosine Antagonists on Distinct Aspects of Motivated Behavior: Interaction with Ethanol and Dopamine Depletion
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The Adenosinergic System a Non-Dopaminergic Target in Parkinson’S Disease
springer.com Biomedicine : Neurosciences Morelli, M., Simola, N., Wardas, J. (Eds.) The Adenosinergic System A Non-Dopaminergic Target in Parkinson’s Disease Comprehensive book that discusses all the aspects of this class of drugs in relation to Parkinson's Disease Includes a review on the history of istradefylline Includes a review on urate as a biomarker and neuroprotectant Adenosine A2A receptor antagonists have shown great promise in the treatment of Parkinson's Disease and alleviation of symptoms. This bookaddresses various aspects of this class of drugs from their chemical development to their clinical use. Among the many insightful chapters contained in this book, there are three unique reviews that have not previously been published in any format: (1) a history of istradefylline, the first A2A antagonist approved for treatment of Parkinson's Disease, (2) an overview of neuroimaging studies in human death and disease and (3) a study of urate as a possible biomarker and neuroprotectant. Springer 1st ed. 2015, XII, 337 p. 41 Order online at springer.com/booksellers 1st illus., 31 illus. in color. Springer Nature Customer Service Center LLC edition 233 Spring Street New York, NY 10013 USA Printed book T: +1-800-SPRINGER NATURE Hardcover (777-4643) or 212-460-1500 [email protected] Printed book Hardcover ISBN 978-3-319-20272-3 $ 199,99 Available Discount group Professional Books (2) Product category Contributed volume Series Current Topics in Neurotoxicity Other renditions Softcover ISBN 978-3-319-37186-3 Softcover ISBN 978-3-319-20274-7 Prices and other details are subject to change without notice. -
Caffeine and Adenosine
Journal of Alzheimer’s Disease 20 (2010) S3–S15 S3 DOI 10.3233/JAD-2010-1379 IOS Press Review Article Caffeine and Adenosine Joaquim A. Ribeiro∗ and Ana M. Sebastiao˜ Institute of Pharmacology and Neurosciences, Faculty of Medicine and Unit of Neurosciences, Institute of Molecular Medicine, University of Lisbon, Lisbon, Portugal Abstract. Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine. Keywords: Adenosine, Alzheimer’s disease, anxiety, caffeine, cognition, Huntington’s disease, migraine, Parkinson’s disease, schizophrenia, sleep INTRODUCTION were considered out of the scope of the present work. For more detailed analysis of the actions of caffeine in Caffeine causes most of its biological effects via humans, namely cognition, dementia, and Alzheimer’s antagonizing all types of adenosine receptors (ARs). -
Effects of Tianeptine on Onset Time of Pentylenetetrazole-Induced Seizures in Mice: Possible Role of Adenosine A1 Receptors
Neuropsychopharmacology (2007) 32, 412–416 & 2007 Nature Publishing Group All rights reserved 0893-133X/07 $30.00 www.neuropsychopharmacology.org Effects of Tianeptine on Onset Time of Pentylenetetrazole-Induced Seizures in Mice: Possible Role of Adenosine A1 Receptors ,1 1 1 Tayfun I Uzbay* , Hakan Kayir and Mert Ceyhan 1Department of Medical Pharmacology, Psychopharmacology Research Unit, Gulhane Military Medical Academy, Ankara, Turkey Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss–Webster mice (25–35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5–80 mg/kg, i.p.) or saline administration. The onset times of ‘first myoclonic jerk’ (FMJ) and ‘generalized clonic seizures’ (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10–60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. -
Caspase-1-Dependent Inflammatory Signaling in Retinal Müller Cells During the Development of Diabetic Retinopathy
CASPASE-1-DEPENDENT INFLAMMATORY SIGNALING IN RETINAL MüLLER CELLS DURING THE DEVELOPMENT OF DIABETIC RETINOPATHY by KATHERINE EILEEN TRUEBLOOD Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Dissertation Advisor: Dr. George R. Dubyak Department of Physiology and Biophysics CASE WESTERN RESERVE UNIVERSITY January 2012 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Katherine Eileen Trueblood ______________________________________________________ Doctor of Philosophy candidate for the ________________________________degree *. Dr. Corey Smith (signed)_______________________________________________ (chair of the committee) Dr. George R. Dubyak ________________________________________________ Dr. Thomas McCormick ________________________________________________ Dr. Patrick Wintrode ________________________________________________ Dr. Margaret Chandler ________________________________________________ Dr. Thomas Nosek ________________________________________________ 10/21/11 (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. ii DEDICATION I dedicate this work to my brother, Jonathan Vern Trueblood, as he embarks on his own graduate school career this year. There will be many days where you will want to give up and throw in the towel; but I promise there will be many more to come where you will be glad you didn’t. Rom. 4:18-21 Always “hope against hope!” iii TABLE -
Inosine Binds to A3 Adenosine Receptors and Stimulates Mast Cell Degranulation
Inosine binds to A3 adenosine receptors and stimulates mast cell degranulation. X Jin, … , B R Duling, J Linden J Clin Invest. 1997;100(11):2849-2857. https://doi.org/10.1172/JCI119833. Research Article We investigated the mechanism by which inosine, a metabolite of adenosine that accumulates to > 1 mM levels in ischemic tissues, triggers mast cell degranulation. Inosine was found to do the following: (a) compete for [125I]N6- aminobenzyladenosine binding to recombinant rat A3 adenosine receptors (A3AR) with an IC50 of 25+/-6 microM; (b) not bind to A1 or A2A ARs; (c) bind to newly identified A3ARs in guinea pig lung (IC50 = 15+/-4 microM); (d) lower cyclic AMP in HEK-293 cells expressing rat A3ARs (ED50 = 12+/-5 microM); (e) stimulate RBL-2H3 rat mast-like cell degranulation (ED50 = 2.3+/-0.9 microM); and (f) cause mast cell-dependent constriction of hamster cheek pouch arterioles that is attenuated by A3AR blockade. Inosine differs from adenosine in not activating A2AARs that dilate vascular smooth muscle and inhibit mast cell degranulation. The A3 selectivity of inosine may explain why it elicits a monophasic arteriolar constrictor response distinct from the multiphasic dilator/constrictor response to adenosine. Nucleoside accumulation and an increase in the ratio of inosine to adenosine may provide a physiologic stimulus for mast cell degranulation in ischemic or inflamed tissues. Find the latest version: https://jci.me/119833/pdf Inosine Binds to A3 Adenosine Receptors and Stimulates Mast Cell Degranulation Xiaowei Jin,* Rebecca K. Shepherd,‡ Brian R. Duling,‡ and Joel Linden‡§ *Department of Biochemistry, ‡Department of Molecular Physiology and Biological Physics, and §Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908 Abstract Mast cells are found in the lung where they release media- tors that constrict bronchiolar smooth muscle. -
Adenosine Challenge Information for Patients Your Doctor Has Recommended That You Have an Adenosine Challenge
Adenosine challenge Information for patients Your doctor has recommended that you have an adenosine challenge. The purpose of this test is to see if you have an accessory pathway called ‘Wolff-Parkinson-White (WPW) syndrome’. What is an accessory pathway? This is an extra electrical connection between the top chambers (atria) and bottom chambers (ventricles) of the heart. This extra electrical connection may allow electrical signals to bypass the normal route in your heart and form a short circuit. This can result in your heart beating abnormally fast for periods of time, which is called supra-ventricular tachycardia (SVT). This is not usually dangerous, but can cause unpleasant symptoms, such as a racing heart (palpitations), dizziness, chest pain, shortness of breath or, rarely, may cause you to collapse. Although the extra connection is present from birth (congenital), symptoms may not develop until later in life. In some cases, WPW syndrome may be life-threatening, particularly if it occurs alongside a type of irregular heartbeat called atrial fibrillation. However, this is rare and treatment can completely remove this risk. page 2 How is an accessory pathway diagnosed? Adenosine is the drug used in this test. It belongs to a group of medicines called anti-arrhythmics. Adenosine blocks electrical signals through the atrio-ventricular (AV) node. This means signals cannot travel from the top to the bottom chambers of the heart for a few seconds, until the drug effects wear off. If an accessory pathway (extra connection) is present, the electrical signals can still travel down to the ventricles, and this will show up on the ECG. -
DEMAND REDUCTION a Glossary of Terms
UNITED NATIONS PUBLICATION Sales No. E.00.XI.9 ISBN: 92-1-148129-5 ACKNOWLEDGEMENTS This document was prepared by the: United Nations International Drug Control Programme (UNDCP), Vienna, Austria, in consultation with the Commonwealth of Health and Aged Care, Australia, and the informal international reference group. ii Contents Page Foreword . xi Demand reduction: A glossary of terms . 1 Abstinence . 1 Abuse . 1 Abuse liability . 2 Action research . 2 Addiction, addict . 2 Administration (method of) . 3 Adverse drug reaction . 4 Advice services . 4 Advocacy . 4 Agonist . 4 AIDS . 5 Al-Anon . 5 Alcohol . 5 Alcoholics Anonymous (AA) . 6 Alternatives to drug use . 6 Amfetamine . 6 Amotivational syndrome . 6 Amphetamine . 6 Amyl nitrate . 8 Analgesic . 8 iii Page Antagonist . 8 Anti-anxiety drug . 8 Antidepressant . 8 Backloading . 9 Bad trip . 9 Barbiturate . 9 Benzodiazepine . 10 Blood-borne virus . 10 Brief intervention . 11 Buprenorphine . 11 Caffeine . 12 Cannabis . 12 Chasing . 13 Cocaine . 13 Coca leaves . 14 Coca paste . 14 Cold turkey . 14 Community empowerment . 15 Co-morbidity . 15 Comprehensive Multidisciplinary Outline of Future Activities in Drug Abuse Control (CMO) . 15 Controlled substance . 15 Counselling and psychotherapy . 16 Court diversion . 16 Crash . 16 Cross-dependence . 17 Cross-tolerance . 17 Custody diversion . 17 Dance drug . 18 Decriminalization or depenalization . 18 Demand . 18 iv Page Demand reduction . 19 Dependence, dependence syndrome . 19 Dependence liability . 20 Depressant . 20 Designer drug . 20 Detoxification . 20 Diacetylmorphine/Diamorphine . 21 Diuretic . 21 Drug . 21 Drug abuse . 22 Drug abuse-related harm . 22 Drug abuse-related problem . 22 Drug policy . 23 Drug seeking . 23 Drug substitution . 23 Drug testing . 24 Drug use . -
Advances in Non-Dopaminergic Treatments for Parkinson's Disease
REVIEW ARTICLE published: 22 May 2014 doi: 10.3389/fnins.2014.00113 Advances in non-dopaminergic treatments for Parkinson’s disease Sandy Stayte 1,2 and Bryce Vissel 1,2* 1 Neuroscience Department, Neurodegenerative Disorders Laboratory, Garvan Institute of Medical Research, Sydney, NSW, Australia 2 Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia Edited by: Since the 1960’s treatments for Parkinson’s disease (PD) have traditionally been directed Eero Vasar, University of Tartu, to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic Estonia L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has Reviewed by: resulted in extensive efforts to develop new therapies that work in ways other than Andrew Harkin, Trinity College Dublin, Ireland restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic Sulev Kõks, University of Tartu, therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, Estonia and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron Pille Taba, Universoty of Tartu, chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a Estonia Pekka T. Männistö, University of detailed account of their success in animal models and their translation to human clinical Helsinki, Finland trials. We then consider how advances in understanding the mechanisms of PD, genetics, *Correspondence: the possibility that PD may consist of multiple disease states, understanding of the Bryce Vissel, Neuroscience etiology of PD in non-dopaminergic regions as well as advances in clinical trial design Department, Neurodegenerative will be essential for ongoing advances. We conclude that despite the challenges ahead, Disorders Laboratory, Garvan Institute of Medical Research, patients have much cause for optimism that novel therapeutics that offer better disease 384 Victoria Street, Darlinghurst, management and/or which slow disease progression are inevitable. -
Lethality of Adenosine for Cultured Mammalian Cells by Interference with Pyrimidine Biosynthesis
J. Cell Set. 13, 429-439 (i973) 429 Printed in Great Britain LETHALITY OF ADENOSINE FOR CULTURED MAMMALIAN CELLS BY INTERFERENCE WITH PYRIMIDINE BIOSYNTHESIS K. ISHII* AND H. GREEN Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, U.S.A. SUMMARY Adenosine at low concentration is toxic to mammalian cells in culture. This may escape notice because some sera (such as calf or human) commonly used in culture media, contain adenosine deaminase. In the absence of serum deaminase, adenosine produced inhibition of growth of a number of established cell lines at concentrations as low as 5 x io~* M, and killed at 2 x io~5 M. This effect required the presence of cellular adenosine kinase, since a mutant line deficient in this enzyme was 70-fold less sensitive to adenosine. The toxic substance is therefore derived from adenosine by phosphorylation, and is probably one of the adenosine nucleotides. The toxic effect of adenosine in concentrations up to 2 x io~* M was completely prevented by the addition of uridine or of pyrimidines potentially convertible to uridine, suggesting that the adenosine was interfering with endogenous synthesis of uridylate. In the presence of adenosine, the conversion of labelled aspartate to uridine nucleotides was reduced by 80-85 %> and labelled orotate accumulated in both the cells and in the culture medium. The lethality of adenosine results from inhibition by one of its nucleotide products of the synthesis of uridylate at the stage of phosphoribosylation of orotate. INTRODUCTION Though adenosine is not an intermediate on the endogenous pathway of purine biosynthesis, it can be efficiently utilized through the purine salvage pathways as the sole purine source in cultured mammalian cells whose endogenous purine synthesis is blocked by aminopterin (Green & Ishii, 1972). -
Neuronal Adenosine A2A Receptors Signal Ergogenic Effects of Caffeine
www.nature.com/scientificreports OPEN Neuronal adenosine A2A receptors signal ergogenic efects of cafeine Aderbal S. Aguiar Jr1,2*, Ana Elisa Speck1,2, Paula M. Canas1 & Rodrigo A. Cunha1,3 Cafeine is one of the most used ergogenic aid for physical exercise and sports. However, its mechanism of action is still controversial. The adenosinergic hypothesis is promising due to the pharmacology of cafeine, a nonselective antagonist of adenosine A1 and A2A receptors. We now investigated A2AR as a possible ergogenic mechanism through pharmacological and genetic inactivation. Forty-two adult females (20.0 ± 0.2 g) and 40 male mice (23.9 ± 0.4 g) from a global and forebrain A2AR knockout (KO) colony ran an incremental exercise test with indirect calorimetry (V̇O2 and RER). We administered cafeine (15 mg/kg, i.p., nonselective) and SCH 58261 (1 mg/kg, i.p., selective A2AR antagonist) 15 min before the open feld and exercise tests. We also evaluated the estrous cycle and infrared temperature immediately at the end of the exercise test. Cafeine and SCH 58621 were psychostimulant. Moreover, Cafeine and SCH 58621 were ergogenic, that is, they increased V̇O2max, running power, and critical power, showing that A2AR antagonism is ergogenic. Furthermore, the ergogenic efects of cafeine were abrogated in global and forebrain A2AR KO mice, showing that the antagonism of A2AR in forebrain neurons is responsible for the ergogenic action of cafeine. Furthermore, cafeine modifed the exercising metabolism in an A2AR-dependent manner, and A2AR was paramount for exercise thermoregulation. Te natural plant alkaloid cafeine (1,3,7-trimethylxantine) is one of the most common ergogenic substances for physical activity practitioners and athletes 1–10. -
Inosine in Biology and Disease
G C A T T A C G G C A T genes Review Inosine in Biology and Disease Sundaramoorthy Srinivasan 1, Adrian Gabriel Torres 1 and Lluís Ribas de Pouplana 1,2,* 1 Institute for Research in Biomedicine, Barcelona Institute of Science and Technology, 08028 Barcelona, Catalonia, Spain; [email protected] (S.S.); [email protected] (A.G.T.) 2 Catalan Institution for Research and Advanced Studies, 08010 Barcelona, Catalonia, Spain * Correspondence: [email protected]; Tel.: +34-934034868; Fax: +34-934034870 Abstract: The nucleoside inosine plays an important role in purine biosynthesis, gene translation, and modulation of the fate of RNAs. The editing of adenosine to inosine is a widespread post- transcriptional modification in transfer RNAs (tRNAs) and messenger RNAs (mRNAs). At the wobble position of tRNA anticodons, inosine profoundly modifies codon recognition, while in mRNA, inosines can modify the sequence of the translated polypeptide or modulate the stability, localization, and splicing of transcripts. Inosine is also found in non-coding and exogenous RNAs, where it plays key structural and functional roles. In addition, molecular inosine is an important secondary metabolite in purine metabolism that also acts as a molecular messenger in cell signaling pathways. Here, we review the functional roles of inosine in biology and their connections to human health. Keywords: inosine; deamination; adenosine deaminase acting on RNAs; RNA modification; translation Citation: Srinivasan, S.; Torres, A.G.; Ribas de Pouplana, L. Inosine in 1. Introduction Biology and Disease. Genes 2021, 12, 600. https://doi.org/10.3390/ Inosine was one of the first nucleobase modifications discovered in nucleic acids, genes12040600 having been identified in 1965 as a component of the first sequenced transfer RNA (tRNA), tRNAAla [1]. -
Alcohol Responsibly and Ending Tobacco Use, Plus Caffeine - Dr
MHE-110 – Chapter Nine – Drinking Alcohol Responsibly and Ending Tobacco Use, plus Caffeine - Dr. Dave Shrock Chapter Nine Alcohol - an overview Alcohol and ending Tobacco Use 13th pp. 239-240; 12th pp. 232-223 • alcohol is the most widely used drug in the United (including caffeine) States • 86% of Americans consume alcohol 13th edition, pp. • 10% are heavy drinkers…who consume half of all the 241-269 alcohol produced 12th edition: • no other form of addiction or disability costs the US pp. 231-261 more than alcohol use/abuse annually Excessive alcohol use causes 88,000 deaths annually (chapter eight) twice as many as illicit drugs • lost work time, illness, insurance, accidents, medical costs take a toll on all of us…25% of all medical costs in the US are alcohol related Alcohol: The world’s most what is alcohol? dangerous drug? 13th, pp. 239-240; 12th pp. 232-233 The Lancet Medical Journal - 1 November, 2016 • alcohol is a byproduct of fermentation • In a recent article published in of vegetable or fruit pulp or ‘mash’ the British medical journal The this produces a concentration of Lancet, when considering the alcohol up to 14% drug’s damage to: • distillation is a further process by •one’s self capturing the vapors from heating • one’s family the mash, and mix this with water • the environment • proof is the measure of % of alcohol, which means the % • economic cost of alcohol is half of the ‘proof rating’ • Alcohol is the world’s most • some alcohol is 152 proof, or 71% alcohol most beers are damaging drug to individuals 8 proof, or 4% alcohol.