REGULATION of the ENDOGENOUS OPIOID SYSTEM by ACUTE NICOTINE and NICOTINE WITHDRAWAL DISSERTATION Presented in Partial Fulfillme
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Analytical Performance of an Immunoassay to Measure Proenkephalin ⁎ Leslie J
Clinical Biochemistry xxx (xxxx) xxx–xxx Contents lists available at ScienceDirect Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem Analytical performance of an immunoassay to measure proenkephalin ⁎ Leslie J. Donatoa, ,Jeffrey W. Meeusena, John C. Lieskea, Deborah Bergmannc, Andrea Sparwaßerc, Allan S. Jaffea,b a Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States b Division of Cardiology, Mayo Clinic, Rochester, MN 55905, United States c Sphingotec GmbH, Hennigsdorf, Germany ARTICLE INFO ABSTRACT Keywords: Background: Endogenous opioids, enkephalins, are known to increase with acute kidney injury. Since the mature Biomarkers pentapeptides are unstable, we evaluated the performance of an assay that measures proenkephalin 119–159 Proenkephalin (PENK), a stable peptide formed concomitantly with mature enkephalins. Enkephalin Methods: PENK assay performance was evaluated on two microtiterplate/chemiluminescence sandwich im- Pro-enkephalin munoassay formats that required 18 or 1 h incubation times. PENK concentration was measured in plasma from penKid healthy individuals to establish a reference interval and in patients with varied levels of kidney function and Assay validation comorbidities to assess the association with measured glomerular filtration rate (mGFR) using iothalamate clearance. Results: Assay performance characteristics in plasma were similar between the assay formats. Limit of quanti- tation was 26.0 pmol/L (CV = 20%) for the 1 h assay and 17.3 pmol/L (CV = 3%) for the 18 h assay. Measurable ranges were 26–1540 pmol/L (1 h assay) and 18–2300 pmol/L (18 h assay). PENK concentrations are stable in plasma stored ambient to 10 days, refrigerated to at least 15 days, and frozen to at least 90 days. -
Information to Users
The direct and modulatory antinociceptive actions of endogenous and exogenous opioid delta agonists Item Type text; Dissertation-Reproduction (electronic) Authors Vanderah, Todd William. Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 04/10/2021 00:14:57 Link to Item http://hdl.handle.net/10150/187190 INFORMATION TO USERS This ~uscript }las 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 mannscript 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, beginnjng at the upper left-hand comer and contimJing 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. -
Enkephalin Degradation in Serum of Patients with Inflammatory Bowel Diseases
Pharmacological Reports 71 (2019) 42–47 Contents lists available at ScienceDirect Pharmacological Reports journal homepage: www.elsevier.com/locate/pharep Original article Enkephalin degradation in serum of patients with inflammatory bowel diseases a, a b Beata Wilenska *, Dagmara Tymecka , Marcin Włodarczyk , b c Aleksandra Sobolewska-Włodarczyk , Maria Wisniewska-Jarosinska , d e b a,d, Jolanta Dyniewicz , Árpád Somogyi , Jakub Fichna , Aleksandra Misicka * a Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warszawa, Poland b Department of Biochemistry, Medical University of Lodz, Łódz, Poland c Department of Gastroenterology, Medical University of Lodz, Łódz, Poland d Department of Neuropeptides, Mossakowski Medical Research Centre Polish Academy of Science, Warszawa, Poland e Campus Chemical Instrumentation Centre (CCIC), The Ohio State University, Columbus, OH, USA A R T I C L E I N F O A B S T R A C T Article history: Background: Inflammatory bowel diseases (IBD) are a group of chronic and recurrent gastrointestinal Received 18 April 2018 disorders that are difficult to control. Recently, a new IBD therapy based on the targeting of the Received in revised form 10 June 2018 endogenous opioid system has been proposed. Consequently, due to the fact that endogenous Accepted 1 August 2018 enkephalins have an anti-inflammatory effect, we aimed at investigating the degradation of serum Available online 2 August 2018 enkephalin (Met- and Leu-enkephalin) in patients with IBD. Methods: Enkephalin degradation in serum of patients with IBD was characterized using mass Keywords: spectrometry methods. Calculated half-life (T1/2) of enkephalins were compared and correlated with the Inflammatory bowel diseases disease type and gender of the patients. -
Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O
pharmaceutics Article Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O-Desmethyltramadol Pharmacokinetic Profiles in a Korean Population Using Physiologically-Based Pharmacokinetic Modeling Hyeon-Cheol Jeong 1, Soo Hyeon Bae 2 , Jung-Woo Bae 3, Sooyeun Lee 3, Anhye Kim 4 , Yoojeong Jang 1 and Kwang-Hee Shin 1,* 1 College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea; [email protected] (H.-C.J.); [email protected] (Y.J.) 2 Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea; [email protected] 3 College of Pharmacy, Keimyung University, Daegu 42601, Korea; [email protected] (J.-W.B.); [email protected] (S.L.) 4 Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-53-950-8582 Received: 6 October 2019; Accepted: 15 November 2019; Published: 17 November 2019 Abstract: Tramadol is a µ-opioid receptor agonist and a monoamine reuptake inhibitor. O-desmethyltramadol (M1), the major active metabolite of tramadol, is produced by CYP2D6. A physiologically-based pharmacokinetic model was developed to predict changes in time-concentration profiles for tramadol and M1 according to dosage and CYP2D6 genotypes in the Korean population. Parallel artificial membrane permeation assay was performed to determine tramadol permeability, and the metabolic clearance of M1 was determined using human liver microsomes. Clinical study data were used to develop the model. Other physicochemical and pharmacokinetic parameters were obtained from the literature. Simulations for plasma concentrations of tramadol and M1 (after 100 mg tramadol was administered five times at 12-h intervals) were based on a total of 1000 virtual healthy Koreans using SimCYP® simulator. -
ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update
The ASAM NATIONAL The ASAM National Practice Guideline 2020 Focused Update Guideline 2020 Focused National Practice The ASAM PRACTICE GUIDELINE For the Treatment of Opioid Use Disorder 2020 Focused Update Adopted by the ASAM Board of Directors December 18, 2019. © Copyright 2020. American Society of Addiction Medicine, Inc. All rights reserved. Permission to make digital or hard copies of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for commercial, advertising or promotional purposes, and that copies bear this notice and the full citation on the fi rst page. Republication, systematic reproduction, posting in electronic form on servers, redistribution to lists, or other uses of this material, require prior specifi c written permission or license from the Society. American Society of Addiction Medicine 11400 Rockville Pike, Suite 200 Rockville, MD 20852 Phone: (301) 656-3920 Fax (301) 656-3815 E-mail: [email protected] www.asam.org CLINICAL PRACTICE GUIDELINE The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update 2020 Focused Update Guideline Committee members Kyle Kampman, MD, Chair (alpha order): Daniel Langleben, MD Chinazo Cunningham, MD, MS, FASAM Ben Nordstrom, MD, PhD Mark J. Edlund, MD, PhD David Oslin, MD Marc Fishman, MD, DFASAM George Woody, MD Adam J. Gordon, MD, MPH, FACP, DFASAM Tricia Wright, MD, MS Hendre´e E. Jones, PhD Stephen Wyatt, DO Kyle M. Kampman, MD, FASAM, Chair 2015 ASAM Quality Improvement Council (alpha order): Daniel Langleben, MD John Femino, MD, FASAM Marjorie Meyer, MD Margaret Jarvis, MD, FASAM, Chair Sandra Springer, MD, FASAM Margaret Kotz, DO, FASAM George Woody, MD Sandrine Pirard, MD, MPH, PhD Tricia E. -
Opioids and Nicotine Dependence in Planarians
Pharmacology, Biochemistry and Behavior 112 (2013) 9–14 Contents lists available at ScienceDirect Pharmacology, Biochemistry and Behavior journal homepage: www.elsevier.com/locate/pharmbiochembeh Opioid receptor types involved in the development of nicotine physical dependence in an invertebrate (Planaria)model Robert B. Raffa a,⁎, Steve Baron a,b, Jaspreet S. Bhandal a,b, Tevin Brown a,b,KevinSongb, Christopher S. Tallarida a,b, Scott M. Rawls b a Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA b Department of Pharmacology & Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA article info abstract Article history: Recent data suggest that opioid receptors are involved in the development of nicotine physical dependence Received 18 May 2013 in mammals. Evidence in support of a similar involvement in an invertebrate (Planaria) is presented using Received in revised form 18 September 2013 the selective opioid receptor antagonist naloxone, and the more receptor subtype-selective antagonists CTAP Accepted 21 September 2013 (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH )(μ, MOR), naltrindole (δ, DOR), and nor-BNI (norbinaltorphimine) Available online 29 September 2013 2 (κ, KOR). Induction of physical dependence was achieved by 60-min pre-exposure of planarians to nicotine and was quantified by abstinence-induced withdrawal (reduction in spontaneous locomotor activity). Known MOR Keywords: Nicotine and DOR subtype-selective opioid receptor antagonists attenuated the withdrawal, as did the non-selective Abstinence antagonist naloxone, but a KOR subtype-selective antagonist did not. An involvement of MOR and DOR, but Withdrawal not KOR, in the development of nicotine physical dependence or in abstinence-induced withdrawal was thus Physical dependence demonstrated in a sensitive and facile invertebrate model. -
PRODUCT INFORMATION Spinorphin Item No
PRODUCT INFORMATION Spinorphin Item No. 29914 NH CAS Registry No.: 137201-62-8 Formal Name: L-leucyl-L-valyl-L-valyl-L-tyrosyl-L- O H O N prolyl-L-tryptophyl-L-threonine N OH O N H Synonyms: Leu-Val-Val-Tyr-Pro-Trp-Thr, O OH H LVVYPWT O O N MF: C45H64N8O10 N N O FW: 877.0 H H NH2 Purity: ≥95% UV/Vis.: λmax: 222 nm Supplied as: A crystalline solid Storage: -20°C OH Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Spinorphin is supplied as a crystalline solid. A stock solution may be made by dissolving the spinorphin in the solvent of choice, which should be purged with an inert gas. Spinorphin is soluble in organic solvents such as DMSO and dimethyl formamide. The solubility of spinorphin in these solvents is approximately 30 mg/ml. Description Spinorphin is a heptapeptide inhibitor of the enkephalin-degrading enzymes aminopeptidase, dipeptidyl aminopeptidase, angiotensin-converting enzyme (ACE), and enkephalinase (IC50s = 3.3, 1.4, 2.4, and 10 µg/ml, respectively, for monkey brain enzymes).1 It is selective for these enzymes over human serum aminopeptidase A (IC50 = >100 µg/ml), as well as porcine kidney aminopeptidase B, aminopeptidase M, dipeptidyl peptidase 1 (DPP-1), DPP-2, DPP-3, and DPP-4 (IC50s = >55 µg/ml for all). Spinorphin inhibits chemotaxis, production of reactive oxygen species (ROS), and exocytosis of glucuronidase and collagenase in polymorphonuclear neutrophils (PMNs). It potentiates enkephalin-induced action potentials in rat hippocampal slices. -
Identification of Β-Endorphins in the Pituitary Gland and Blood Plasma Of
271 Identification of -endorphins in the pituitary gland and blood plasma of the common carp (Cyprinus carpio) E H van den Burg, J R Metz, R J Arends, B Devreese1, I Vandenberghe1, J Van Beeumen1, S E Wendelaar Bonga and G Flik Department of Animal Physiology, Faculty of Science, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands 1Laboratory of Protein Biochemistry and Protein Engineering, University of Gent, KL Ledeganckstraat 35, B9000 Gent, Belgium (Requests for offprints should be addressed to G Flik; Email: gertfl[email protected]) Abstract Carp -endorphin is posttranslationally modified by N-acetyl -endorphin(1–29) and these forms together N-terminal acetylation and C-terminal cleavage. These amounted to over 50% of total immunoreactivity. These processes determine the biological activity of the products were partially processed to N-acetyl - -endorphins. Forms of -endorphin were identified in endorphin(1–15) (30·8% of total immunoreactivity) and the pars intermedia and the pars distalis of the pituitary N-acetyl -endorphin(1–10) (3·1%) via two different gland of the common carp (Cyprinus carpio), as well as the cleavage pathways. The acetylated carp homologues of forms released in vitro and into the blood. After separation mammalian - and -endorphin were also found. and quantitation by high performance liquid chroma- N-acetyl -endorphin(1–15) and (1–29) and/or (1–33) tography (HPLC) coupled with radioimmunoassay, the were the major products to be released in vitro, and were -endorphin immunoreactive products were identified by the only acetylated -endorphins found in blood plasma, electrospray ionisation mass spectrometry and peptide although never together. -
Antitumor Activity of Actinonin in Vitro and in Vivo
Vol. 4, 171-176, January 1998 Clinical Cancer Research 171 Antitumor Activity of Actinonin in Vitro and in Vivo Yang Xu, Lawrence T. Lai, Janice L. Gabrilove, 8), mye!oid and monocytic cells, and most myeloblastic leuke- and David A. Scheinberg’ mias as well as on cells and tissues outside the hematopoietic system including fibroblasts, intestinal epithelium, renal tubular Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 epithelium, and synaptic membranes of the central nervous system (I ). APN occurs as a homodimer, and the molecule is a 150-kDa, transmembrane glycoprotein with an intracellular ABSTRACT amino terminus (1). F23, an antihuman CD13/APN mAb, is able Actinonin, an antibiotic and CD13/aminopeptidase N to completely block the active site of the enzyme (9). (APN) inhibitor, has been shown to be cytotoxic to tumor Bestatin, a CD 1 3/APN inhibitor, was examined in preclin- cell lines in vitro. We investigated the antiproliferative ef- ical and clinical studies; bestatin could inhibit lymph node fects of actinonin on human and murine leukemia and lym- metastasis of P388 leukemia in mice (10) and was used in phoma cells. Actinonin inhibited growth of NB4 and HL6O clinical trials in malignant skin tumors (1 1), in head and neck human cell lines and AKR mouse leukemia cells in vitro with cancer (12), in esophageal cancer (13), and in gynecologic an IC50 of about 2-S g/ml. The inhibitory effect on CD13- tumors (14). High doses of bestatin resulted in the significant positive cells was not blocked by pretreatment with the inhibition of preexisting experimental and spontaneous metas- anti-CD13/APN monoclonal antibody F23, which binds with tasis in mice (15). -
Biased Signaling by Endogenous Opioid Peptides
Biased signaling by endogenous opioid peptides Ivone Gomesa, Salvador Sierrab,1, Lindsay Lueptowc,1, Achla Guptaa,1, Shawn Goutyd, Elyssa B. Margolise, Brian M. Coxd, and Lakshmi A. Devia,2 aDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; bDepartment of Physiology & Biophysics, Virginia Commonwealth University, Richmond, VA 23298; cSemel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095; dDepartment of Pharmacology & Molecular Therapeutics, Uniformed Services University, Bethesda MD 20814; and eDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94143 Edited by Susan G. Amara, National Institutes of Health, Bethesda, MD, and approved April 14, 2020 (received for review January 20, 2020) Opioids, such as morphine and fentanyl, are widely used for the possibility that endogenous opioid peptides could vary in this treatment of severe pain; however, prolonged treatment with manner as well (13). these drugs leads to the development of tolerance and can lead to For opioid receptors, studies showed that mice lacking opioid use disorder. The “Opioid Epidemic” has generated a drive β-arrestin2 exhibited enhanced and prolonged morphine-mediated for a deeper understanding of the fundamental signaling mecha- antinociception, and a reduction in side-effects, such as devel- nisms of opioid receptors. It is generally thought that the three opment of tolerance and acute constipation (15, 16). This led to types of opioid receptors (μ, δ, κ) are activated by endogenous studies examining whether μOR agonists exhibit biased signaling peptides derived from three different precursors: Proopiomelano- (17–20), and to the identification of agonists that preferentially cortin, proenkephalin, and prodynorphin. -
Screening of 109 Neuropeptides on Asics Reveals No Direct Agonists
www.nature.com/scientificreports OPEN Screening of 109 neuropeptides on ASICs reveals no direct agonists and dynorphin A, YFMRFamide and Received: 7 August 2018 Accepted: 14 November 2018 endomorphin-1 as modulators Published: xx xx xxxx Anna Vyvers, Axel Schmidt, Dominik Wiemuth & Stefan Gründer Acid-sensing ion channels (ASICs) belong to the DEG/ENaC gene family. While ASIC1a, ASIC1b and ASIC3 are activated by extracellular protons, ASIC4 and the closely related bile acid-sensitive ion channel (BASIC or ASIC5) are orphan receptors. Neuropeptides are important modulators of ASICs. Moreover, related DEG/ENaCs are directly activated by neuropeptides, rendering neuropeptides interesting ligands of ASICs. Here, we performed an unbiased screen of 109 short neuropeptides (<20 amino acids) on fve homomeric ASICs: ASIC1a, ASIC1b, ASIC3, ASIC4 and BASIC. This screen revealed no direct agonist of any ASIC but three modulators. First, dynorphin A as a modulator of ASIC1a, which increased currents of partially desensitized channels; second, YFMRFamide as a modulator of ASIC1b and ASIC3, which decreased currents of ASIC1b and slowed desensitization of ASIC1b and ASIC3; and, third, endomorphin-1 as a modulator of ASIC3, which also slowed desensitization. With the exception of YFMRFamide, which, however, is not a mammalian neuropeptide, we identifed no new modulator of ASICs. In summary, our screen confrmed some known peptide modulators of ASICs but identifed no new peptide ligands of ASICs, suggesting that most short peptides acting as ligands of ASICs are already known. Acid-sensing ion channels form a small family of proton-gated ion channels that belongs to the degenerin/epi- thelial Na+ channel (DEG/ENaC) gene family1. -
Medications for Opioid Use Disorder for Healthcare and Addiction Professionals, Policymakers, Patients, and Families
Medications for Opioid Use Disorder For Healthcare and Addiction Professionals, Policymakers, Patients, and Families UPDATED 2020 TREATMENT IMPROVEMENT PROTOCOL TIP 63 Please share your thoughts about this publication by completing a brief online survey at: https://www.surveymonkey.com/r/KAPPFS The survey takes about 7 minutes to complete and is anonymous. Your feedback will help SAMHSA develop future products. TIP 63 MEDICATIONS FOR OPIOID USE DISORDER Treatment Improvement Protocol 63 For Healthcare and Addiction Professionals, Policymakers, Patients, and Families This TIP reviews three Food and Drug Administration-approved medications for opioid use disorder treatment—methadone, naltrexone, and buprenorphine—and the other strategies and services needed to support people in recovery. TIP Navigation Executive Summary For healthcare and addiction professionals, policymakers, patients, and families Part 1: Introduction to Medications for Opioid Use Disorder Treatment For healthcare and addiction professionals, policymakers, patients, and families Part 2: Addressing Opioid Use Disorder in General Medical Settings For healthcare professionals Part 3: Pharmacotherapy for Opioid Use Disorder For healthcare professionals Part 4: Partnering Addiction Treatment Counselors With Clients and Healthcare Professionals For healthcare and addiction professionals Part 5: Resources Related to Medications for Opioid Use Disorder For healthcare and addiction professionals, policymakers, patients, and families MEDICATIONS FOR OPIOID USE DISORDER TIP 63 Contents