DOCSLIB.ORG

Furnished a Hint of Qualitative Differences. Perhaps the First Of

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Furnished a Hint of Qualitative Differences. Perhaps the First Of 314 J. Physiol. (1958) I44, 3I4-336 THE ACTION OF SYMPATHOMIMETIC AMINES IN ANIMALS TREATED WITH RESERPINE BY J. H. BURN AND M. J. RAND From the Department of Pharmacology, University of Oxford (Received 3 June 1958) The impression left in the minds of those who have read the account of the sympathomimetic amines written by Barger & Dale in 1910 has been that these substances in the main were found to differ only quantitatively in activity. From time to time, however, there have been observations which furnished a hint of qualitative differences. Perhaps the first of these was the discovery by Tainter & Chang (1927) that under the influence of cocaine the action of tyramine was abolished, although, as Frohlich & Loewi had shown in 1910, the action of adrenaline was potentiated. In 1931 Burn & Tainter ob- served that tyramine and ephedrine had no action on the denervated pupil, though to adrenaline it was supersensitive. In 1932, Burn recorded that denervation of the cat's foreleg by removal of the stellate ganglion led to a loss of the vasoconstrictor action of tyramine and of ephedrine, though not of that of adrenaline. Burn also found that in the perfused dog's hind leg tyramine and ephedrine had, compared with adrenaline, only a fraction of the constrictor action they would be expected to have, judging from the pressor effect in the spinal cat. He observed, however, that the constrictor action could be restored if adrenaline was added to the blood perfusing the hind leg, and that this restoration could not be effected by adding pituitary (posterior lobe) extract instead. Fleckenstein & Burn (1953) found that after denervation of the nictitating membrane it became more sensitive only to those amines which were catechol derivatives; that to the derivatives of phenylethanolamine it was less sensitive and to the derivatives of phenylethylamine it was nearly insensitive. Flecken- stein & Bass (1953) and Fleckenstein & St6ckle (1955) showed that the nor- mally innervated nictitating membrane after full doses of cocaine behaved in exactly the same way. These various observations have remained incoordinated and unexplained. Recently, however, Carlsson, Rosengren, Bertler & Nilsson (1957) found that, in cats treated with reserpine, the intravenous injection of tyramine had no SYMPATHOMIMETIC AMINES 315 pressor effect. In explanation they said that 'tyramine belongs to a group of sympathomimetic amines which are fully active only in the presence of an intact adrenergic system'. We have recently observed (Burn & Rand, 1957, 1958b) that when rabbits and dogs were treated with reserpine, the noradrena- line-like substance demonstrated by Schmiterl6w (1948) to be present in the wall of the aorta disappeared. We also observed that the constrictor action of nicotine in the perfused rabbit's ear disappeared, and were led to the con- clusion that nicotine exerted this constrictor action by releasing a noradrena- line-like substance from the vessel wall or perhaps from chromaffin cells in its neighbourhood. It therefore seemed to us possible that the failure of tyramine to exert its pressor action in the cat after treatment with reserpine was due to the fact that tyramine normally acted by releasing a noradrenaline-like substance from the vessel walls. We now describe experiments to test the action of a series of sympathomimetic amines from this point of view. METHODS Observations of four kinds have been made. The effect of sympathomimetic amines has been examined (1) on the blood pressure, the spleen and the nictitating membrane of the spinal cat; (2) on the arterial resistance and venous outflow of the perfused dog hind leg; (3) on the outflow of the perfused rabbit ear; and (4) on spiral strips of rabbit aorta set up in an isolated organ bath. Spinal cats were prepared under ether anaesthesia, dividing the cord at the 2nd cervical verte- bra and destroying the brain. Records of the spleen volume and of the contractions of the nicti- tating membrane were made as described by Burn (1952). For the hind leg perfusion one dog was bled under ether anaesthesia from the carotid artery into a jar containing heparin, and its lungs were prepared for perfusion by one of a pair of Dale-Schuster (1928) pumps. Perfusion was begun through the lungs, which were ventilated by oxygen with 5 % CO2. A second dog was then anaes- thetized. After dividing the rectum and the inferior mesenteric artery between ligatures, the right external iliac artery was tied, and a cannula was inserted pointing towards the aorta. The body wall was divided in sections between ligatures along the course ofthe left external iliac artery. Poupart's ligament was cut. Branches of the left external iliac from the aorta to about 1 cm below Poupart's ligament were tied, as were also the corresponding veins. The continuation of the aorta below the origin of the external iliac arteries was tied. When the dissection was complete, perfusion was begun by the second pump through the left hind leg at the moment of tying the aorta to arrest the natural circulation. In some experiments the left lumbar sympathetic chain was prepared for stimulation; in these the dog was first eviscerated and the left kidney removed. After the arrest of the natural circula- tion, the dog was cut in half, the perfusing cannula was tied into the aorta and the blood collected from the vena cava. By this method the ganglia of the sympathetic chain were perfused. In these experiments there was an interval of 7 min between the arrest of the natural circulation and the start of the perfusion. In all perfusions mass ligatures were tied so as to enclose the whole circumference of the body wall above the area perfused. An outflow record was obtained by using Stephenson's recorder (1949). When stimulating the sympathetic chain shielded electrodes, each a silver plate 3 mm wide, were used; stimuli were square-wave pulses of 2-5 mA strength, 1 msec duration and 20-25/sec frequency. The perfusion of the rabbit ear was arranged as previously described (Burn, 1952) using Stephen- son's outflow recorder (1948). 316 J. H. BURN AND M. J. RAND Reserpine was dissolved in 20% ascorbic acid solution making the solution up to 10 mg/ml. as required. Injections were made intraperitoneally. Dogs were given 0-5 mg/kg on two successive days, the dog being killed on the third day. Cats were given 2-5-5-0 mg/kg on two successive days, and rabbits were given 3 mg/kg on two successive days. Fig. 1. Upper record is that of the nictitating membrane; lower record that of blood pressure in the spinal preparation. (a) Normal cat; injection of 10 i&g noradrenaline produced a small rise of blood pressure; 4 mg tyramine hydrochloride produced a large rise of blood pressure and large contraction of the nictitating membrane. (b) Cat treated with reserpine. Note that the effects were reversed; 4 mg tyramine had a very slight effect on the blood pressure and none on the nictitating membrane; 10 iLg noradrenaline had a large effect on the blood pressure. (c) Same as (b); after the intravenous infusion of 0-12 mg noradrenaline, the effect of 4 mg tyramine on the blood pressure was much greater than in (b). RESULTS Action of tyramine Fig. 1 shows records taken from experiments in two spinal cats, the one a normal cat, and the second a cat treated with reserpine. In Fig. 1la the injection of 10 pg noradrenaline into the normal cat caused a small rise of blood pressure, whereas the injection of 4 mg tyramine hydrochloride caused a large rise of blood pressure and a large contraction of the nictitating mem- brane. In Fig. 1lb the same injections were made into a cat treated with reserpine. The effect of 4 mg tyramine hydrochloride was very small and there was no contraction of the nictitating membrane, while the effect of 10 pg noradrenaline was very much larger than in the normal cat. A solution of SYMPATHOMIMETIC AMINES 317 noradrenaline was then prepared in a burette and the burette was connected to the femoral vein. An infusion of noradrenaline at a uniform rate was begun and maintained until 012 mg noradrenaline had entered the cat. The infusion caused a large rise of blood pressure, but although the rate of infusion was kept constant, the blood pressure fell as the infusion continued, though the extent of this fall varied in different experiments. At the end of the infu- sion the point at which the blood pressure returned to its former level was noted, and an injection of 4 mg tyramine was made again, as shown in Fig. 1 c. Fig. 2. Upper record is that of the spleen volume; lower record that of blood pressure, in the spinal preparation. (a) Normal cat. (b) Cat, treated with reserpine, in which 2 tg adrenaline had a greater effect on the spleen volume than 10 jg in (a), and in which 1 mg tyramine had no action, though it contracted the spleen in (a). An infusion ofnoradrenaline was then made, after which (c) 1 mg tyramine again caused contraction. The rise of blood pressure was much greater than in Fig. 1 b and there was also a small contraction of the nictitating membrane which was absent in Fig. 1 b. The events shown in Fig. 1 were observed in many experiments. When the pressor action of tyramine had been restored, as in Fig. 1 c, then repeated injections of tyramine had a declining effect, but a further infusion of nor- adrenaline would restore it a second time. In other experiments the spleen volume was recorded, as shown in Fig.
Load more

Recommended publications
  • 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 ........................................................................................................................................................................
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Tyramine and Amyloid Beta 42: a Toxic Synergy
    biomedicines Article Tyramine and Amyloid Beta 42: A Toxic Synergy Sudip Dhakal and Ian Macreadie * School of Science, RMIT University, Bundoora, VIC 3083, Australia; [email protected] * Correspondence: [email protected]; Tel.: +61-3-9925-6627 Received: 5 May 2020; Accepted: 27 May 2020; Published: 30 May 2020 Abstract: Implicated in various diseases including Parkinson’s disease, Huntington’s disease, migraines, schizophrenia and increased blood pressure, tyramine plays a crucial role as a neurotransmitter in the synaptic cleft by reducing serotonergic and dopaminergic signaling through a trace amine-associated receptor (TAAR1). There appear to be no studies investigating a connection of tyramine to Alzheimer’s disease. This study aimed to examine whether tyramine could be involved in AD pathology by using Saccharomyces cerevisiae expressing Aβ42. S. cerevisiae cells producing native Aβ42 were treated with different concentrations of tyramine, and the production of reactive oxygen species (ROS) was evaluated using flow cytometric cell analysis. There was dose-dependent ROS generation in wild-type yeast cells with tyramine. In yeast producing Aβ42, ROS levels generated were significantly higher than in controls, suggesting a synergistic toxicity of Aβ42 and tyramine. The addition of exogenous reduced glutathione (GSH) was found to rescue the cells with increased ROS, indicating depletion of intracellular GSH due to tyramine and Aβ42. Additionally, tyramine inhibited the respiratory growth of yeast cells producing GFP-Aβ42, while there was no growth inhibition when cells were producing GFP. Tyramine was also demonstrated to cause increased mitochondrial DNA damage, resulting in the formation of petite mutants that lack respiratory function.
    [Show full text]
  • 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
    [Show full text]
  • 212102Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 212102Orig1s000 OTHER REVIEW(S) Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research | Office of Surveillance and Epidemiology (OSE) Epidemiology: ARIA Sufficiency Date: June 29, 2020 Reviewer: Silvia Perez-Vilar, PharmD, PhD Division of Epidemiology I Team Leader: Kira Leishear, PhD, MS Division of Epidemiology I Division Director: CAPT Sukhminder K. Sandhu, PhD, MPH, MS Division of Epidemiology I Subject: ARIA Sufficiency Memo for Fenfluramine-associated Valvular Heart Disease and Pulmonary Arterial Hypertension Drug Name(s): FINTEPLA (Fenfluramine hydrochloride, ZX008) Application Type/Number: NDA 212102 Submission Number: 212102/01 Applicant/sponsor: Zogenix, Inc. OSE RCM #: 2020-953 The original ARIA memo was dated June 23, 2020. This version, dated June 29, 2020, was amended to include “Assess a known serious risk” as FDAAA purpose (per Section 505(o)(3)(B)) to make it consistent with the approved labeling. The PMR development template refers to the original memo, dated June 23, 2020. Page 1 of 13 Reference ID: 46331494640015 EXECUTIVE SUMMARY (place “X” in appropriate boxes) Memo type -Initial -Interim -Final X X Source of safety concern -Peri-approval X X -Post-approval Is ARIA sufficient to help characterize the safety concern? Safety outcome Valvular Pulmonary heart arterial disease hypertension (VHD) (PAH) -Yes -No X X If “No”, please identify the area(s) of concern. -Surveillance or Study Population X X -Exposure -Outcome(s) of Interest X X -Covariate(s) of Interest X X -Surveillance Design/Analytic Tools Page 2 of 13 Reference ID: 46331494640015 1.
    [Show full text]
  • Information to Users
    INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. University Microfilms International A Bell & Howell Information C om pany 300 North Z eeb Road. Ann Arbor. Ml 48106-1346 USA 313/761-4700 800 521-0600 Order Number 9120692 Part 1. Synthesis of fiuorinated catecholamine derivatives as potential adrenergic stimulants and thromboxane A 2 antagonists. Part 2.
    [Show full text]
  • The Enigma of Conditioned Taste Aversion Learning: Stimulus Properties of 2-Phenylethylamine Derivatives
    Physiol. Res. 51: S13-S19, 2002 The Enigma of Conditioned Taste Aversion Learning: Stimulus Properties of 2-phenylethylamine Derivatives A. J. GREENSHAW1, S. TURKISH2, B. A. DAVIS2 1Neurochemical Research Unit, Department of Psychiatry, University of Alberta and 2Neuropsychiatric Research Unit, University of Saskatchewan, Canada Summary The functional aversive stimulus properties of several IP doses of (±)-amphetamine (1.25-10 mg.kg-1), 2-phenylethylamine (PEA, 2.5-10 mg.kg-1, following inhibition of monoamine oxidase with pargyline 50 mg.kg-1) and phenylethanolamine (6.25-50 mg.kg-1) were measured with the conditioned taste aversion (CTA) paradigm. A two-bottle choice procedure was used, water vs. 0.1 % saccharin with one conditioning trial and three retention trials. (±)-Amphetamine and phenylethanolamine induced a significant conditioned taste aversion but PEA did not. (±)-Amphetamine and PEA increased spontaneous locomotor activity but phenylethanolamine had no effects on this measure. Measurement of whole brain levels of these drugs revealed that the peak brain elevation of PEA occurred at approximately 10 min whereas the peak elevations of (±)-amphetamine and phenylethanolamine occurred at approximately 20 min. The present failure of PEA to elicit conditioned taste aversion learning is consistent with previous reports for this compound. The differential functional aversive stimulus effects of these three compounds are surprising since they exhibit similar discriminative stimulus properties and both (±)-amphetamine and PEA are self- administered by laboratory animals. The present data suggest that time to maximal brain concentrations following peripheral injection may be a determinant of the aversive stimulus properties of PEA derivatives. Key words 2-phenylethylamine • (±)-amphetamine • Phenylethanolamine • Conditioned taste aversion • Locomotor activity • Drug levels Introduction (Greenshaw et al.
    [Show full text]
  • The Role of Norepinephrine in the Pharmacology of 3,4
    !"#$%&'#$&($)&*#+,-#+"*,-#$,-$."#$/"0*102&'&34$&($ 56789#."4'#-#:,&;41#."01+"#.01,-#$<9=9>6$?#[email protected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`,E#-E$ I0--$ D-.#*$ 2*#0.,J#2&11&-@X&*3a',2#-2#@aY48-28 -:aSX]a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
    [Show full text]
  • Principles-Of-Autonomic-Medicine-V
    Principles of Autonomic Medicine v. 2.1 DISCLAIMERS This work was produced as an Official Duty Activity while the author was an employee of the United States Government. The text and original figures in this book are in the public domain and may be distributed or copied freely. Use of appropriate byline or credit is requested. For reproduction of copyrighted material, permission by the copyright holder is required. The views and opinions expressed here are those of the author and do not necessarily state or reflect those of the United States Government or any of its components. References in this book to specific commercial products, processes, services by trade name, trademark, manufacturer, or otherwise do not necessarily constitute or imply their endorsement, recommendation, or favoring by the United States Government or its employees. The appearance of external hyperlinks is provided with the intent of meeting the mission of the National Institute of Neurological Disorders and Stroke. Such appearance does not constitute an endorsement by the United States Government or any of its employees of the linked web sites or of the information, products or services contained at those sites. Neither the United States Government nor any of its employees, including the author, exercise any editorial control over the information that may be found on these external sites. Permission was obtained from the following for reproduction of pictures in this book. Other reproduced pictures were from -- 1 -- Principles of Autonomic Medicine v. 2.1 Wikipedia Commons or had no copyright. Tootsie Roll Industries, LLC (Tootsie Roll Pop, p. 26) Dr. Paul Greengard (portrait photo, p.
    [Show full text]
  • Demonstration and Distribution of Phenylethanolamine in Brain And
    Proc. Nat. Acad. Sci. USA Vol. 70, No. 3, pp. 769-772, March 1973 Demonstration and Distribution of Phenylethanolamine in Brain and Other Tissues (enzyme assay/intraneural synthesis and storage/phenylethylamine/phenylalanine/rat) JUAN M. SAAVEDRA AND JULIUS AXELROD Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20014 Contributed by Julius Axelrod, December 26, 1972 ABSTRACT A specific and sensitive assay for phenyl- of a mixture containing 10 ul of partially purified phenyl- ethanolamine in tissues is described. By this assay, phenyl- ethanolamine was detected in many peripheral tissues and ethanolamine N-methyltransferase, 5 Ml (0.54 nmol) of brains of rats. It is unequally distributed in rat brain, with [3H]methyl-S-adenosyl-l-methionine (specific activity, 4.54 the highest concentration present in hypothalamus and Ci/mmol) and 35 ul of 20 mM Tris * HCl buffer (pH 8.6). 1 ng midbrain. Concentrations of brain phenylethanolamine of phenylethanolamine was added to another aliquot as an were elevated after administration of phenylethylamine, internal standard. The incubation was stopped by addition of phenylalanine, p-chlorophenylalanine, and monoamine oxidase inhibitors and decreased after administration of 0.5 ml of 0.5 M borate buffer (pH 10) and the radioactive dopamine-fl-hydroxylase inhibitors. Denervation of sym- product was extracted with 6 ml of a mixture containing 95% pathetic nerves caused a moderate fall in phenylethanol- heptane and 5% isoamyl alcohol (v/v), by shaking for 15 sec. amine concentrations. These results indicate that phenyl- After the phases were separated by centrifugation, a 5-ml ethanolamine is synthesized intraneuronally from phenyl- alanine and phenylethylamine, but that only part of the aliquot of the organic phase was transferred to counting vials phenylethanolamine is stored in sympathetic nerves.
    [Show full text]