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Dynamic Regulation of Synaptic GABA Release by the Glutamate-Glutamine Cycle in Hippocampal Area CA1
The Journal of Neuroscience, August 16, 2006 • 26(33):8537–8548 • 8537 Development/Plasticity/Repair Dynamic Regulation of Synaptic GABA Release by the Glutamate-Glutamine Cycle in Hippocampal Area CA1 Shu-Ling Liang,1 Gregory C. Carlson,1 and Douglas A. Coulter1,2 1Division of Neurology and the Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia, and 2Departments of Pediatrics, Neurology, and Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 Vesicular GABA and intraterminal glutamate concentrations are in equilibrium, suggesting inhibitory efficacy may depend on glutamate availability. Two main intraterminal glutamate sources are uptake by neuronal glutamate transporters and glutamine synthesized through the astrocytic glutamate-glutamine cycle. We examined the involvement of the glutamate-glutamine cycle in modulating GABAergic synaptic efficacy. In the absence of neuronal activity, disruption of the glutamate-glutamine cycle by blockade of neuronal glutamine transport with ␣-(methylamino) isobutyric acid (MeAIB; 5 mM) or inhibition of glutamine synthesis in astrocytes with methionine sulfoximine (MSO; 1.5 mM) had no effect on miniature IPSCs recorded in hippocampal area CA1 pyramidal neurons. How- ever, after a period of moderate synaptic activity, application of MeAIB, MSO, or dihydrokainate (250 M; an astrocytic glutamate transporter inhibitor) significantly reduced evoked IPSC (eIPSC) amplitudes. The MSO effect could be reversed by exogenous application of glutamine (5 mM), whereas glutamine could not rescue the eIPSC decreases induced by the neuronal glutamine transporter inhibitor MeAIB. The activity-dependent reduction in eIPSCs by glutamate-glutamine cycle blockers was accompanied by an enhanced blocking effect of the low-affinity GABAA receptor antagonist, TPMPA [1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid], consistent with diminished GABA release. -
Methionine Sulfoximine: a Novel Anti Inflammatory Agent
Wayne State University Wayne State University Dissertations January 2018 Methionine Sulfoximine: A Novel Anti Inflammatory Agent Tyler Peters Wayne State University, [email protected] Follow this and additional works at: https://digitalcommons.wayne.edu/oa_dissertations Part of the Biochemistry Commons Recommended Citation Peters, Tyler, "Methionine Sulfoximine: A Novel Anti Inflammatory Agent" (2018). Wayne State University Dissertations. 2124. https://digitalcommons.wayne.edu/oa_dissertations/2124 This Open Access Dissertation is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Dissertations by an authorized administrator of DigitalCommons@WayneState. METHIONINE SULFOXIMINE: A NOVEL ANTI-INFLAMMATORY AGENT by TYLER J. PETERS DISSERTATION Submitted to the Graduate School of Wayne State University – School of Medicine Detroit, Michigan in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOHPY 2018 MAJOR: BIOCHEMISTRY & MOL. BIOLOGY Approved By: __________________________________________ Advisor Date DEDICATION This work is dedicated to my family. I wouldn’t have made it this far without your unconditional love and support. ii ACKNOWLEDGEMENTS Thank you Dr. Brusilow, I consider myself very fortunate for having the privilege of working in the laboratory of Dr. William S.A. Brusilow these past few years. Under his mentorship, my scientific autonomy was always respected, and my opinions were always valued with consideration. I am thankful for his guidance and support as an advisor; I truly admire his patience and envy his calm demeanor. He exemplifies scientific integrity, and his dedication to develop MSO has inspired me. I had never experienced consistent failure in any aspect of life before encountering scientific research; at times I felt that Dr. -
Glutamate and GABA Dynamics in Early Ischaemia of Rat
J. Physiol. (2002). 543.P Research Symposium – Mechanisms of Ischaemic Cell Death 25S ATP occurring in ischaemia may prevent a protective uptake of glutamate into glia in early ischaemia: with glutamine synthetase Glutamate and GABA dynamics in early ischaemia of rat inhibited, uptake of only a little glutamate released from neurons hippocampal slices may be sufficient to raise [glutamate]i in glia sufficiently to D. Attwell, N.J. Allen, M. Hamman and D.J. Rossi inhibit further uptake. Department of Physiology, University College London, Gower Street, Hamann, M. et al. (2002). Eur. J. Neurosci. 15, 308–314. London WC1E 6BT, UK Rossi, D.J. et al. (2000). Nature 403, 316–321. During brain ischaemia, the run-down of transmembrane ion gradients caused by the fall of ATP levels occurring leads to a rise This work was supported by The Wellcome Trust. in extracellular glutamate and GABA concentrations. The rise of glutamate concentration triggers neuronal death. In simulated All procedures accord with current local guidelines. ischaemia of hippocampal slices, taken from rats humanely killed in accordance with UK animal use legislation, we have used receptors in whole-cell patch-clamped CA1 pyramidal cells to sense released glutamate and GABA. ECl was set to 0 mV, so that currents mediated by ionotropic GABA receptors were inward, Cation channels: a radical way of killing cells and membrane current was recorded at _30 mV to allow glutamate sensing by NMDA and AMPA receptors. Mike Ashford On applying superfusion solution mimicking the energy University of Dundee deprivation occurring during severe ischaemia (no oxygen and glucose, cyanide and iodoacetate present), a slow small increase of inward current occurred over the first few minutes, followed by a sudden massive inward current (nanoamps) which then sagged back to a less inward plateau (Rossi et al. -
Aldrich Raman
Aldrich Raman Library Listing – 14,033 spectra This library represents the most comprehensive collection of FT-Raman spectral references available. It contains many common chemicals found in the Aldrich Handbook of Fine Chemicals. To create the Aldrich Raman Condensed Phase Library, 14,033 compounds found in the Aldrich Collection of FT-IR Spectra Edition II Library were excited with an Nd:YVO4 laser (1064 nm) using laser powers between 400 - 600 mW, measured at the sample. A Thermo FT-Raman spectrometer (with a Ge detector) was used to collect the Raman spectra. The spectra were saved in Raman Shift format. Aldrich Raman Index Compound Name Index Compound Name 4803 ((1R)-(ENDO,ANTI))-(+)-3- 4246 (+)-3-ISOPROPYL-7A- BROMOCAMPHOR-8- SULFONIC METHYLTETRAHYDRO- ACID, AMMONIUM SALT PYRROLO(2,1-B)OXAZOL-5(6H)- 2207 ((1R)-ENDO)-(+)-3- ONE, BROMOCAMPHOR, 98% 12568 (+)-4-CHOLESTEN-3-ONE, 98% 4804 ((1S)-(ENDO,ANTI))-(-)-3- 3774 (+)-5,6-O-CYCLOHEXYLIDENE-L- BROMOCAMPHOR-8- SULFONIC ASCORBIC ACID, 98% ACID, AMMONIUM SALT 11632 (+)-5-BROMO-2'-DEOXYURIDINE, 2208 ((1S)-ENDO)-(-)-3- 97% BROMOCAMPHOR, 98% 11634 (+)-5-FLUORODEOXYURIDINE, 769 ((1S)-ENDO)-(-)-BORNEOL, 99% 98+% 13454 ((2S,3S)-(+)- 11633 (+)-5-IODO-2'-DEOXYURIDINE, 98% BIS(DIPHENYLPHOSPHINO)- 4228 (+)-6-AMINOPENICILLANIC ACID, BUTANE)(N3-ALLYL)PD(II) CL04, 96% 97 8167 (+)-6-METHOXY-ALPHA-METHYL- 10297 ((3- 2- NAPHTHALENEACETIC ACID, DIMETHYLAMINO)PROPYL)TRIPH 98% ENYL- PHOSPHONIUM BROMIDE, 12586 (+)-ANDROSTA-1,4-DIENE-3,17- 99% DIONE, 98% 13458 ((R)-(+)-2,2'- 963 (+)-ARABINOGALACTAN BIS(DIPHENYLPHOSPHINO)-1,1'- -
Analytical Method Developments of Antibody Drug Conjugates And
Analytical method developments of antibody drug conjugates and disease biomarkers in microdialysis samples By Yunan Wang Submitted to the graduate degree program in Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. ________________________________ Chairperson Dr. Susan Lunte ________________________________ Dr. Heather Desaire ________________________________ Dr. Julie Stenken ________________________________ Dr. Robert Dunn ________________________________ Dr. Zhuo Wang Date Defended: January 27th, 2016 The Dissertation Committee for Yunan Wang certifies that this is the approved version of the following dissertation: Analytical method developments of antibody drug conjugates and disease biomarkers in microdialysis samples ________________________________ Chairperson Dr. Susan Lunte Date approved: February 1st, 2016 ii Abstract This dissertation focuses on developing analytical methods to study biomarkers in different pharmaceutical samples. Three different analytical methods were developed for microdialysis samples and antibody drug conjugates as anti-tumor drug. The first part of this dissertation is to develop a capillary electrophoresis with laser induced fluorescence (CE-LIF) method to monitor the change of amino acids in rat brain microdialysate as biomarkers of oxidative stress in epileptic seizures. Ornithine and citrulline was successfully separated and quantified. 3-Mercaptopropionic acid (3- MPA) was administrated to rat brain hippocampus region as a convulsant to induce epileptic seizures to free-moving rats. An increase of citrulline and ornithine level was observed after the seizure, and this confirmed nitric oxide were produced in epileptic seizures. In the second project, a high-performance liquid chromatography with mass spectrometry (HPLC-MS) method is developed to simultaneously monitor the change of 13 eicosanoids as biomarkers in rat colon microdialysate to study the enzymatic pathways of inflammatory bowel disease. -
Pharmacological Studies on a Locust Neuromuscular Preparation
J. Exp. Biol. (1974). 6i, 421-442 421 *&ith 2 figures in Great Britain PHARMACOLOGICAL STUDIES ON A LOCUST NEUROMUSCULAR PREPARATION BY A. N. CLEMENTS AND T. E. MAY Woodstock Research Centre, Shell Research Limited, Sittingbourne, Kent {Received 13 March 1974) SUMMARY 1. The structure-activity relationships of agonists of the locust excitatory neuromuscular synapse have been reinvestigated, paying particular attention to the purity of compounds, and to the characteristics and repeatability of the muscle response. The concentrations of compounds required to stimu- late contractions of the retractor unguis muscle equal in force to the neurally evoked contractions provided a measure of the relative potencies. 2. Seven amino acids were capable of stimulating twitch contractions, glutamic acid being the most active, the others being analogues or derivatives of glutamic or aspartic acid. Aspartic acid itself had no excitatory activity. 3. Excitatory activity requires possession of two acidic groups, separated by two or three carbon atoms, and an amino group a to a carboxyl. An L-configuration appears essential. The w-acidic group may be a carboxyl, sulphinyl or sulphonyl group. Substitution of any of the functional groups generally causes total loss of excitatory activity, but an exception is found in kainic acid in which the nitrogen atom forms part of a ring. 4. The investigation of a wide variety of compounds revealed neuro- muscular blocking activity among isoxazoles, hydroxylamines, indolealkyl- amines, /?-carbolines, phenazines and phenothiazines. No specific antagonist of the locust glutamate receptor was found, but synaptic blocking agents of moderately high activity are reported. INTRODUCTION The study of arthropod neuromuscular physiology has been impeded by the lack of an antagonist which can be used to block excitatory synaptic transmission by a specific postsynaptic effect. -
Cerilliant Reference Standards Brochure
QUALITY FOR LIFE Certified Reference Materials for Clinical Testing Merck KGaA Certified Reference Materials (CRMs) are manufactured and certified to the highest industry standards including: • ISO Guide 34 • ISO 17025 • ISO 17043 • ISO 13485 • ISO 9001 • GMP The life science business of Merck KGaA, Darmstadt, Germany operates as MilliporeSigma in the U.S. and Canada. Quality For Life Every test can impact a life Results are only as accurate as your reference Certified Reference Material Categories for Clinical Applications of Testosterone in Serum for • Amino Acids • Fatty Acids Clinical Research Applications • Analgesics • Hormones • Individual levels of testosterone in – Female stripped serum offered separately • Antibiotics – Male at concentrations ranging from – Neonatal 2 to 2,000 ng/dL • Anticancer Drugs – OH Vitamin D • Certified Reference Material grade • Antidepressants – Thyroid • Suitable for clinical research • Antiepileptics • Interference Mixes applications in the US by • Antifungals • Immunosuppressants liquid chromatography, mass spectrometry • Antipsychotics • Nicotine / Tobacco • Each level ready to use as • Antiretrovirals • Organic Acids a linearity standard or for • Bile Acids calibration verification • Biomarkers • Caffeine-related Drugs • NSAIDs • Cardiac Drugs • Vitamins (including A, • Catecholamines B, C, D, E, & K) To learn more, visit SigmaAldrich.com/standards 2 Product Description Cat. No. Product Description Cat. No. Amino Acids & Metabolites Antibiotics (Continued) Creatinine, Coming Soon C-164-1ML Moxifloxacin -
Ssfiglggfs' Agrafât Wmsêêmm Mapmrnm. Mmm ®Pip S®£«£S
agrafât SSfiglggfS' WmSÊÊmm mapmrnm. MgfNN mmm ®PiPs®£«£s$ mmmmm m : •^-•y.-y l-V./.'^M? ,•• -tâig.:fâ)0&^?3Ï'" ' '-ïfsP&t •«£&£&>£ iL- .W& '^ |®®c (1971) Proceedings of the Third International Conference on Plant Pathogenic Bacteria Âi imp* Proceedings of the Third International Conference on Plant Pathogenic Bacteria, Wageningen, 14-21 April 1971 /v° (5* BIBLIOTHÉEK \ V X^*gENir G Editor: H. P. Maas Geesteranus Centre for Agricultural Publishing and Documentation, Wageningen, 1972 UDC 632.35 ISBN 90 220 0357 4 © Centre for Agricultural Publishing and Documentation (Pudoc), Wageningen, 1972 No part of this book may be reproduced and/or published in any form, by print, photoprint, microfilm or any other means without written permission from the publishers. Printed in the Netherlands by Zuid-Nederlandsche Drukkerij N.V., 's-Hertogenbosch Organizing Committee Drs H. P. Maas Geesteranus (Chairman) Miss Dr E. Billing Dr D. W. Dye Dr D. C. Hildebrand Dr I. Lazar Executive Committee Dr J. G. ten Houten (Chairman) J. Drijver (Secretary/Treasurer) Dr G. J. Saaltink Dr A. de Lange Drs G. H. Boerema Drs H. P. Maas Geesteranus Preface The Third International Conference on Plant Pathogenic Bacteria was organized for those scientists who are working with plant pathogenic bacteria. Their interests include microbiology, biochemistry, physiology, pathology or taxonomy. Consequently the programme of this meeting included a variety of subjects. One of the aims of the conference was to provide general information on current work, so that participants working in one discipline could learn of recent development in others. To achieve this, some sessions were devoted to reviews, combined in sym posia on special topics prepared by specialists. -
Amino Acid Analogues
CHAPTER 1 Amino Acid Analogues William Shive and Charles G. Skinner I. Introduction 2 II. Amino Acid Antagonists 3 A. Aromatic Amino Acids 4 B. Leucine, Isoleucine, Valine, Alanine, and Glycine Analogues 11 C. Analogues of Sulfur-containing Amino Acids 15 D. Dicarboxylic Amino Acids and Their Amides 17 E. Hydroxy Amino Acids 22 F. Basic Amino Acids and Proline 23 III. Antagonisms among Amino Acids Essential for Protein Synthesis ... 26 A. Natural Antagonisms Involving Aromatic Amino Acids 27 B. Antagonisms Involving Aliphatic Amino Acids 28 C. Antagonisms of Polyfunctional Amino Acids 29 D. Mutation and Amino Acid Antagonisms 30 IV. Biological Studies Involving Amino Acid Inhibitors 31 A. Determination of Type of Inhibition 31 B. Antagonists in the Study of Biochemical Transformations In volving Amino Acids 32 C. Amino Acid Transport 34 D. Utilization of Peptides, Keto Acids, and Related Amino Acid Derivatives 37 E. Amino Acid Analogues in the Study of Protein Synthesis and Related Processes 39 F. Incorporation of Amino Acid Analogues into Proteins 42 G. Activation and Transfer of Amino Acid Analogues to Ribonucleic Acid 44 H. End Product Control Mechanisms 45 I. Enzymic Transformations Involving Amino Acid Analogues 47 J. Amino Acid Analogues and Chemotherapy 53 References 58 1 2 W. SHIVE AND C. G. SKINNER I. INTRODUCTION Although amino acids under certain conditions had been known for a long time to be toxic to growth of certain organisms, specific reversals of inhibitory effects by a particular metabolite have been observed only since 1935. For example, 0-alanine was observed to be potent as a growth- stimulating agent for yeast only in the absence of asparagine, the presence of which was essential for the development of the specific assay in the dis covery of pantothenic acid (1). -
Swelling-Induced Release of Glutamate, Aspartate, and Taurine from Astrocyte Cultures
The Journal of Neuroscience, May 1990, IO@): 1583-l 591 Swelling-Induced Release of Glutamate, Aspartate, and Taurine from Astrocyte Cultures H. K. Kimelberg,1,2,3 S. K. Goderie,’ S. Higman,’ S. Pang,laa and R. A. Waniewski4 ‘Division of Neurosurgery, *Department of PharmacologyiToxicology, 9nterdepartmental Program in Neuroscience, Albany Medical College, Albany, New York 12208, and 4Wadsworth Center for Laboratories and Research, New York State Department 07 Health, Albany, New York 12201 Swelling of primary astrocyte cultures by exposing them to astrocytes seenin a number of pathological states (Kimelberg hypotonic media caused release of label after the cells had and Ransom, 1986), since swelling of isolated cells and many been allowed to accumulate 3H-L-glutamate, 3H-D-aSpattate, vertebrate and invertebrate tissuesis known to lead to the release or 3H-taurine. Comparable release of endogenous L-gluta- of taurine, glutamate, aspartate, and other amino acids as part mate or taurine, as measured by high-pressure liquid chro- of the processof regulatory volume decrease(RVD) by which matography (HPLC), was also found. Release of label was swollen cells regain their normal volume (Gilles et al., 1987). not affected by treating the cells with cytochalasin B, indi- The pathological conditions in which astroglial swelling is cating that microfilament polymerization was not signifi- observed include experimental (Barron et al., 1988) and human cantly involved. Hypotonic-induced release did not appear (Castejon, 1980) closed head injury, traumatic (stab wound) to principally involve reversal of the Na+-dependent uptake brain edema(Gerschenfeld et al., 1959), ischemia (Garcia et al., system since increasing external K+ to depolarize the cells 1977; Jenkins et al., 1984) hypoglycemia and status epilepticus by replacement of external Na+, thus maintaining isotonic (Siesjo, 1981) prolonged hypoxia (Yu et al., 1972), acute hy- conditions, increased release to a lesser extent. -
Prestwick Collection
(-) -Levobunolol hydrochloride (-)-Adenosine 3',5'-cyclic monophosphate (-)-Cinchonidine (-)-Eseroline fumarate salt (-)-Isoproterenol hydrochloride (-)-MK 801 hydrogen maleate (-)-Quinpirole hydrochloride (+) -Levobunolol hydrochloride (+)-Isoproterenol (+)-bitartrate salt (+,-)-Octopamine hydrochloride (+,-)-Synephrine (±)-Nipecotic acid (1-[(4-Chlorophenyl)phenyl-methyl]-4-methylpiperazine) (cis-) Nanophine (d,l)-Tetrahydroberberine (R) -Naproxen sodium salt (R)-(+)-Atenolol (R)-Propranolol hydrochloride (S)-(-)-Atenolol (S)-(-)-Cycloserine (S)-propranolol hydrochloride 2-Aminobenzenesulfonamide 2-Chloropyrazine 3-Acetamidocoumarin 3-Acetylcoumarin 3-alpha-Hydroxy-5-beta-androstan-17-one 6-Furfurylaminopurine 6-Hydroxytropinone Acacetin Acebutolol hydrochloride Aceclofenac Acemetacin Acenocoumarol Acetaminophen Acetazolamide Acetohexamide Acetopromazine maleate salt Acetylsalicylsalicylic acid Aconitine Acyclovir Adamantamine fumarate Adenosine 5'-monophosphate monohydrate Adiphenine hydrochloride Adrenosterone Ajmalicine hydrochloride Ajmaline Albendazole Alclometasone dipropionate Alcuronium chloride Alexidine dihydrochloride Alfadolone acetate Alfaxalone Alfuzosin hydrochloride Allantoin alpha-Santonin Alprenolol hydrochloride Alprostadil Althiazide Altretamine Alverine citrate salt Ambroxol hydrochloride Amethopterin (R,S) Amidopyrine Amikacin hydrate Amiloride hydrochloride dihydrate Aminocaproic acid Aminohippuric acid Aminophylline Aminopurine, 6-benzyl Amiodarone hydrochloride Amiprilose hydrochloride Amitryptiline hydrochloride -
9: Analytical Standards
CATALOGUE NUMBER 9 ANALYTICAL STANDARDS Table of Contents Standards for Special Applications 3 Standards for Routine Analytical Applications 82 Certified Primary Pharmaceutical Standards 3 Environmental Standards 82 Certified GMO Materials 31 Particle Size Standards 115 Certified Clinical Chemistry Standards 33 Conductivity Standards 116 Other Certified Standards 34 Ion Chromatography Standards 116 Custom & OEM Standards 44 Redox Standards 117 Certified Industrial Raw Materials 44 Forensic & Veterinary Standards 117 Certified Drugs, Metabolites, & Impurities 45 Polymer Standards 126 Certified Food & Agriculture Standards 58 Petrochemical Standards 127 Proficiency Testing for Environmental Analysis 60 AAS/ICP Standards 130 Chromatography & CE Test Mixes 131 Selected Certified Reference Materials 64 TOC Standards 132 Environmental Standards 64 Melting Point Standards 132 Trace Cert Organics 75 Spectroscopy Standards—TraceCert 132 Occupational Hygiene Standards 76 MS Markers 134 Secondary Pharma Standards 76 Pharmaceutical & Clinical Standards 134 Titrimetric Substances 81 X-Ray Standards 135 Certified Spectroscopy Standards 81 Food & Beverage Standards 135 Gravimetry Standards 147 NMR Standards 147 Color Reference Solutions 148 Miscellaneous 148 NOTE: This publication is designed for electronic use only. Hazard and Safety information can be found on product detail pages and at sigma-aldrich.com/safetycenter. 2 Analytical Standards Technical Support: [email protected] Standards for Special Applications Certified Primary Pharmaceutical