D-Serine and D-Cycloserine Reduce Compulsive Alcohol Intake in Rats
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The Role of Agmatine and Arginine Decarboxylase in Ischemic Tolerance After Transient Cerebral Ischemia in Rat Models
The role of agmatine and arginine decarboxylase in ischemic tolerance after transient cerebral ischemia in rat models Jin Young Jung Department of Medicine The Graduate School, Yonsei University The role of agmatine and arginine decarboxylase in ischemic tolerance after transient cerebral ischemia in rat models Directed by Professor Seung Kon Huh The Doctoral Dissertation submitted to the Department of Medicine, the Graduate School of Yonsei University in partial fulfillment of the requirements for the degree of Doctor of Philosophy Jin Young Jung May 2007 This certifies that the Doctoral Dissertation of Jin Young Jung is approved. __________________________________ Thesis Supervisor: Seung Kon Huh __________________________________ Jong Eun Lee: Thesis Committee Member #1 __________________________________ Jin Woo Chang: Thesis Committee Member #2 __________________________________ Duck Sun Ahn: Thesis Committee Member #3 __________________________________ Ji Cheol Shin: Thesis Committee Member #4 The Graduate School Yonsei University May 2007 Acknowledgements Some may consider this short section of the thesis trivial but for me it is a chance to express my sincerest gratitude to those that I am truly thankful. First of all, I would like to express my deepest gratitude to my thesis supervisor and mentor Professor Seung Kon Huh. He has inspired me when I was troubled and always gave me a warm heart. I would also like to thank Professor Jong Eun Lee who shared her valuable time on the execution and interpretation of this study, Professor Jin Woo Chang who always inspiring me with passion and discerning insight. Professor Duck Sun Ahn whose insightful comments were essential in completing this thesis, Professor Ji Cheol Shin for the excellent suggestion for improvement in this thesis. -
Switch to Tonic Discharge by Thyrotropin-Releasing Hormone
Neuron Article Synchronized Network Oscillations in Rat Tuberoinfundibular Dopamine Neurons: Switch to Tonic Discharge by Thyrotropin-Releasing Hormone David J. Lyons,1,* Emilia Horjales-Araujo,1 and Christian Broberger1,* 1Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden *Correspondence: [email protected] (D.J.L.), [email protected] (C.B.) DOI 10.1016/j.neuron.2009.12.024 SUMMARY most common form of pituitary tumor (Burrow et al., 1981), and by the hyperprolactinaemia and sometimes galactorrhea that The pituitary hormone, prolactin, triggers lactation in is a side effect of antipsychotic drugs with DA antagonist prop- nursing mothers. Under nonlactating conditions, erties (Clemens et al., 1974; Meltzer and Fang, 1976). Yet, to prolactin secretion is suppressed by powerful inhibi- date, the cellular and network electrophysiological properties tion from hypothalamic tuberoinfundibular dopamine of the TIDA cell population have not been described. These (TIDA) neurons. Although firing pattern has been sug- factors are potentially fundamental features of prolactin regula- gested as integral to neuroendocrine control, the tion since discharge pattern may determine the functional output of neuroendocrine control of the anterior pituitary, as is observed electrical behavior of TIDA cells remains unknown. in the magnocellular system (Wakerley and Lincoln, 1973; Hatton We demonstrate that rat TIDA neurons discharge et al., 1983). Thus, the periodic bursting pattern in hypothalamic rhythmically in a robust 0.05 Hz oscillation. The oscil- gonadotropin-releasing hormone neurons is required for stimu- lation is phase locked between neurons, and while it lation of target gonadotrophs in the pituitary (Knobil, 1980). persists during chemical synaptic transmission When bursting is artificially replaced by continuous agonist stim- blockade, it is abolished by gap junction antagonists. -
Amino Acid Chemistry
Handout 4 Amino Acid and Protein Chemistry ANSC 619 PHYSIOLOGICAL CHEMISTRY OF LIVESTOCK SPECIES Amino Acid Chemistry I. Chemistry of amino acids A. General amino acid structure + HN3- 1. All amino acids are carboxylic acids, i.e., they have a –COOH group at the #1 carbon. 2. All amino acids contain an amino group at the #2 carbon (may amino acids have a second amino group). 3. All amino acids are zwitterions – they contain both positive and negative charges at physiological pH. II. Essential and nonessential amino acids A. Nonessential amino acids: can make the carbon skeleton 1. From glycolysis. 2. From the TCA cycle. B. Nonessential if it can be made from an essential amino acid. 1. Amino acid "sparing". 2. May still be essential under some conditions. C. Essential amino acids 1. Branched chain amino acids (isoleucine, leucine and valine) 2. Lysine 3. Methionine 4. Phenyalanine 5. Threonine 6. Tryptophan 1 Handout 4 Amino Acid and Protein Chemistry D. Essential during rapid growth or for optimal health 1. Arginine 2. Histidine E. Nonessential amino acids 1. Alanine (from pyruvate) 2. Aspartate, asparagine (from oxaloacetate) 3. Cysteine (from serine and methionine) 4. Glutamate, glutamine (from α-ketoglutarate) 5. Glycine (from serine) 6. Proline (from glutamate) 7. Serine (from 3-phosphoglycerate) 8. Tyrosine (from phenylalanine) E. Nonessential and not required for protein synthesis 1. Hydroxyproline (made postranslationally from proline) 2. Hydroxylysine (made postranslationally from lysine) III. Acidic, basic, polar, and hydrophobic amino acids A. Acidic amino acids: amino acids that can donate a hydrogen ion (proton) and thereby decrease pH in an aqueous solution 1. -
Insights Into the Mn Binding Site in the Agmatinase-Like Protein (ALP): A
International Journal of Molecular Sciences Article Insights into the Mn2+ Binding Site in the Agmatinase-Like Protein (ALP): A Critical Enzyme for the Regulation of Agmatine Levels in Mammals María-Belen Reyes 1, José Martínez-Oyanedel 1,*, Camila Navarrete 1, Erika Mardones 1, Ignacio Martínez 1,Mónica Salas 2, Vasthi López 3, María García-Robles 4, Estefania Tarifeño-Saldivia 1, Maximiliano Figueroa 1, David García 1 and Elena Uribe 1,* 1 Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción 4070386, Chile; [email protected] (M.-B.R.); [email protected] (C.N.); [email protected] (E.M.); [email protected] (I.M.); [email protected] (E.T.-S.); [email protected] (M.F.); [email protected] (D.G.) 2 Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Valdivia 5110566, Chile; [email protected] 3 Departamento de Ciencias Biomédicas, Universidad Católica del Norte, Coquimbo 1781421, Chile; [email protected] 4 Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción 3349001, Chile; [email protected] * Correspondence: [email protected] (J.M.-O.); [email protected] (E.U.) Received: 28 April 2020; Accepted: 5 June 2020; Published: 10 June 2020 Abstract: Agmatine is a neurotransmitter with anticonvulsant, anti-neurotoxic and antidepressant-like effects, in addition it has hypoglycemic actions. Agmatine is converted to putrescine and urea by agmatinase (AGM) and by an agmatinase-like protein (ALP), a new type of enzyme which is present in human and rodent brain tissues. Recombinant rat brain ALP is the only mammalian protein that exhibits significant agmatinase activity in vitro and generates putrescine under in vivo conditions. -
Excitatory Amino Acid Receptor Antagonists and Electroacupuncture Synergetically Inhibit Carrageenan-Induced Behavioral Hyperalgesia and Spinal Fos Expression in Rats
http://www.paper.edu.cn Pain 99 (2002) 525–535 www.elsevier.com/locate/pain Excitatory amino acid receptor antagonists and electroacupuncture synergetically inhibit carrageenan-induced behavioral hyperalgesia and spinal fos expression in rats Yu-Qiu Zhanga, Guang-Chen Jib, Gen-Cheng Wub, Zhi-Qi Zhaoa,* aInstitute of Neurobiology, Fudan University, 220 Han Dan Road, Shanghai, 200433, China bState Key Laboratory of Medical Neurobiology, Medical Center of Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032, China Received 30 January 2002; accepted 27 June 2002 Abstract The interaction between electroacupuncture and an N-methyl-d-aspartic acid (NMDA) receptor antagonist, (DL-2-amino-5-phosphono- pentanoic acid; AP5), or an ( ^ )-a-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainite (AMPA/KA) receptor antagonist, (6,7- dinitroquinoxaline-2,3 (1H,4H); DNQX) administered intrathecally on carrageenan-induced thermal hyperalgesia and spinal c-Fos expres- sion was investigated. The latency of paw withdrawal (PWL) from a thermal stimulus was used as a measure of hyperalgesia in awake rats. Intrathecal (i.t.) injection of 1 and 10 nmol AP5, but not DNQX, markedly increased the PWL of the carrageenan-injected paw. At a dose of 100 nmol, either AP5 or DNQX significantly increased the PWL of carrageenan-injected paw, with AP5 being more potent. The PWLs of the non-injected and normal saline (NS)-injected paws were not detectably affected by the administration of NMDA or AMPA/KA receptor antagonists at the doses tested. Unilateral electroacupuncture stimulation of the ‘Zu-San-Li’ (St 36) and ‘Kun-Lun’ (UB 60) acupuncture points (60 and 2 Hz alternately, 1–2–3 mA) contralateral to the carrageenan-injected paw significantly elevated the PWLs of carrageenan- and NS-injected paws. -
Glutamate but Not Glycine Agonist Affinity for NMDA Receptors Is
The Journal of Neuroscience, April 1, 2002, 22(7):2550–2560 Glutamate But Not Glycine Agonist Affinity for NMDA Receptors Is Influenced by Small Cations Rinat Nahum-Levy,* Eyal Tam,* Sara Shavit, and Morris Benveniste Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, 69978 Israel NMDA receptor currents desensitize in an agonist-dependent extracellular cation prevented the reduction of glutamate affin- manner when either the glutamate or glycine agonist is sub- ity. In addition, the use of choline-, sodium-, or cesium-based saturating. This may result from a conformational change in the intracellular solutions did not alter desensitization characteris- NMDA receptor protein that lowers glutamate and glycine bind- tics, indicating that the site responsible for reduction of gluta- ing site affinity induced by co-agonist binding, channel opening, mate affinity is not in the intracellular domain. The fact that the or ion permeation. We have used whole-cell voltage clamp of reduction of glutamate affinity is dependent on certain small cultured hippocampal neurons with agonist paired-pulse pro- extracellular cations whereas the reduction of glycine affinity is tocols to demonstrate that glutamate and glycine dissociate insensitive to such cations indicates that conformational 7.9- and 6.8-fold slower in the absence of their respective changes induced by the binding of glutamate are not com- co-agonists than when their co-agonists are present. Paired- pletely paralleled by the conformational changes induced by pulse and desensitization protocols were used to show that glycine. Although glutamate and glycine are essential co- co-agonist binding and channel opening are sufficient to cause agonists, these data suggest that they have differential roles in a reduction in glycine affinity, but extracellular sodium or mag- the process of NMDA receptor activation. -
The Biosynthesis of Free Glycine and Serine by Tumors*
The Biosynthesis of Free Glycine and Serine by Tumors* SAULKIT (University of Texas M. D. Anderson Hospital and Tumor Institute, Department of Biochemistry, Houston, Texas) When cell suspensions of the Gardner lympho- Tissues and incubation procedure.—TheGardnerand Mecca sarcoma were incubated with acetate-2-C14, ap lymphosarcomas, previously transplanted to grow as solid tumors, were transformed into ascites tumors. It was observed preciable radioactivity was observed in the alpha that less total radioactivity was found in Gardner ascites carbon of free glycine (4). There are described be tumor glycine after incubations with labeled acetate than in low experiments showing that the methyl carbon the earlier experiments (4), which were carried out with cell of acetate may also be utilized in the formation of suspensions made from the solid tumors. The preparation of free serine. The incorporation of radioactivity cellular suspensions from the solid tumors involves a rather thorough extraction of soluble proteins and endogenous from labeled glucose into both amino acids and of metabolites. Possibly, the difference is partly attributable labeled ribose into glycine is also demonstrated to this factor. (Note, in this connection, Table 4 and Table 5, (5). The latter conversions take place in tumors experiment 1.) However, the observed conversion by the other than the Gardner lymphosarcoma. ascites cells was deemed adequate for our purposes, so that ascites cells were used thereafter. The author proposes the following scheme as a Tumor-bearing -
Cobalamins and Nitrous Oxide: a Review
J Clin Pathol: first published as 10.1136/jcp.33.10.909 on 1 October 1980. Downloaded from J Clin Pathol 1980;33:909-916 Cobalamins and nitrous oxide: a review I CHANARIN From the Department of Haematology, MRC Clinical Research Centre, Harrow, Middlesex, UK The anaesthetic gas, nitrous oxide (N20), once is not more rapid if B12 is supplied, suggesting that regarded as chemically inert, oxidises some forms of new apoenzyme needs to be synthesised. vitamin B12. It does this both when used clinically and in the test tube, and the action is remarkably Clinical observations selective. As far as we know, no other pathway or substance is affected except as a result of damage to The first clinical report of toxicity that could be vitamin B12. Vitamin B12 that has been oxidised in ascribed to N20 was that of Lassen et al. in 1956,3 this way no longer functions as a coenzyme. Thus who used a 50% N20/oxygen mixture as well as other the effect of N20 presents the biochemist and agents to control the spasms in patients with tetanus. haematologist with a remarkable tool with which Treatment was continued for up to six days. Two of to explore the mode of action of vitamin B12. the patients died, and pancytopenias appeared in It presents the neurologist and neuropathologist most of the patients accompanied by megaloblastic with a new probe into the mechanism of vitamin B12 haemopoiesis demonstrated by marrow aspiration. neuropathy, and finally it is a new tool with which The marrow, indeed, was indistinguishable from that to explore the complex field of vitamin B12-folate in untreated pernicious anaemia. -
Oral Population Modeling of L-Serine in Humans
ORIGINAL RESEARCH published: 13 May 2021 doi: 10.3389/fphar.2021.643179 Informing Pharmacokinetic Models With Physiological Data: Oral Population Modeling of L-Serine in Humans J. R. Bosley 1*, Elias Björnson 2,3, Cheng Zhang 4, Hasan Turkez 5, Jens Nielsen 3, Mathias Uhlen 4, Jan Borén 2 and Adil Mardinoglu 4,6* 1Clermont Bosley LLC, Philadelphia, PA, United States, 2Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden, 3Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden, 4Science for Life Laboratory, KTH—Royal Institute of Technology, Stockholm, Sweden, 5Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Turkey, 6Centre for Host–Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London, United Kingdom To determine how to set optimal oral L-serine (serine) dose levels for a clinical trial, existing literature was surveyed. Data sufficient to set the dose was inadequate, and so an (n 10) Edited by: George D Loizou, phase I-A calibration trial was performed, administering serine with and without other oral Health and Safety Laboratory, agents. We analyzed the trial and the literature data using pharmacokinetic (PK) modeling United Kingdom and statistical analysis. The therapeutic goal is to modulate specific serine-related Reviewed by: metabolic pathways in the liver using the lowest possible dose which gives the desired José Augusto Guimarães Morais, Universidade de Lisboa, Portugal effect since the upper bound was expected to be limited by toxicity. A standard PK Amir Sadeghi, approach, in which a common model structure was selected using a fit to data, yielded a University of Eastern Finland, Finland model with a single central compartment corresponding to plasma, clearance from that *Correspondence: J. -
Alcohol Withdrawal Drives Depressive Behaviors by Activating Neurons in the Rostromedial Tegmental Nucleus
Alcohol Withdrawal Drives Depressive Behaviors by Activating Neurons in the Rostromedial Tegmental Nucleus Cite this article as: Rao Fu, Wanhong Zuo, Nimisha Shiwalkar, Qinghua Mei, Qing Fan, Xuejun Chen, Jing Li, Alex Bekker and Jiang-Hong Ye, Alcohol Withdrawal Drives Depressive Behaviors by Activating Neurons in the Rostromedial Tegmental Nucleus, Neuropsychopharmacology doi:10.1038/s41386-019-0378-8 This Author Accepted Manuscript is a PDF file of an unedited peer-reviewed manuscript that has been accepted for publication but has not been copyedited or corrected. The official version of record that is published in the journal is kept up to date and so may therefore differ from this version. Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. https://www.nature.com/authors/policies/license.html#AAMtermsV1 © 2019 American College of Neuropsychopharmacology. All rights reserved. Alcohol Withdrawal Drives Depressive Behaviors by Activating Neurons in the Rostromedial Tegmental Nucleus Rao Fu, Wanhong Zuo, Nimisha Shiwalkar, Qinghua Mei, Qing Fan, Xuejun Chen, Jing Li, Alex Bekker, Jiang-Hong Ye* Department of Anesthesiology, Department of Pharmacology, & Physiology and Neuroscience, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, 07103, USA RF and WZ contribute equally to this work. Corresponding author: Jiang-Hong Ye Department of Anesthesiology, Rutgers, the State University of New Jersey, New Jersey Medical School 185 South Orange Ave, Newark, NJ 07103, USA [email protected] Tel: 973-972-1866 Running title: RMTg in alcohol withdrawal Keywords: dopamine; GABA; nucleus accumbens; chemogenetics; electrophysiology; sucrose preferring test; forced swimming test; functional hemispheric disconnection Abstract: 245 words, Introduction: 330 words, Materials and Methods: 753 words Discussion: 1348 Text total: 4312 (Introduction, Methods, Results, Discussion) # of Figures: 6 # of table 1 # of supplement data: 1 1 © 2019 American College of Neuropsychopharmacology. -
Nomination Background: L-Beta-Methylaminoalanine
Chemical Information Review Document for L-β-Methylaminoalanine [CAS No. 15920-93-1] Supporting Nomination for Toxicological Evaluation by the National Toxicology Program September 2008 National Toxicology Program National Institute of Environmental Health Sciences National Institutes of Health U.S Department of Health and Human Services Research Triangle Park, NC http://ntp.niehs.nih.gov/ Abstract L-β-Methylaminoalanine (L-BMAA) is a neurotoxic non-protein amino acid that is produced by cyanobacteria, a blue-green algae that is common to many lakes, oceans, and soils, and is found in Cycas circinalis seeds. It has previously been associated with the neurological disease amyotrophic lateral sclerosis-Parkinson dementia complex (ALS-PDC) in an indigenous population in Guam. Consumption of tortillas made from cycad-seed flour and of flying foxes (Mariana fruit bats, a "traditional delicacy" in Guam) that feed on cycad fruit has been implicated as the source of L-BMAA exposure. Protein-bound and free L-BMAA have been shown to bioconcentrate in the Guam ecosystem (bacteria, plants, animals, and human tissues) and detectable levels have been measured in brain tissue of people in Guam who suffered from dementia-related disorders. Because it is present in blue-green algae from a variety of water sources around the world and samples of Baltic Sea and oceanic blooms, significant quantities may be released into the world's oceans and water supplies. Studies in primates showed that L-BMAA produced a neurodegenerative syndrome very similar to that of ALS-PDC. Single doses also induced seizures in mice and rats and intracranial injection in mice produced hippocampal damage. -
Studies of Glycine Metabolism and Transport in Fibroblasts from Patients with Nonketotic Hyperglycinemia
Pediatr. Res. 14: 932-934 (1980) fibroblasts nonketotic hyperglycinemia glycine serine metabolism, amino acids valine Na+ transport system Studies of Glycine Metabolism and Transport in Fibroblasts from Patients with Nonketotic Hyperglycinemia DAVID M. HALTON"" AND INGEBORG KRIEGER Wa,vne State Universirv School of Medicine. The Metabolic Service, Department of Pediatrics. Children's Hospital of Michigan, Detroit. Michigan, USA Summary coverslips were rinsed twice with phosphate-buffered saline glu- cose (PBSG) [I30 mM NaCI, 5 mM KCI, 1.2 mM MgS04, 1 mM Glycine transport in both normal and nonketotic hyperglycine- CaC12, 5 mM glucose. and 10 mM Na2HP04(pH 7.4)]. In a final mia fibroblasts was shown to occur by a sodium-dependent system. wash, the coverslips were left for one hr in PBSG at 37OC to No significant difference could be detected in either the Km's (1.4 minimize endogenous glycine levels. to 2.0 mM) or the Vm,'s (6.2 to 16 nmole per mg protein per min) The incubation procedure was similar to that of Foster and of the three control and three patient cell lines. Valine was a weak Pardee (3). Four yl of [2-L4C]glycine (15) were added per ml of competitive inhibitor of glycine uptake. Ki's from both groups fell incubation medium containing PBSG, unlabeled glycine, and, in into the 5.6 to 5.8 mM range. Plasma levels of valine of one patient some studies, valine. Incubations were camed out for 2 min at reached a maximum of 0.6 mM following a valine load. Glycine 37°C.