DOCSLIB.ORG

Celltransmissions Newsletter

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Celltransmissions Newsletter 1 Celltransmissions The Newsletter for Cell Signaling and Neuroscience Research Vol 20, No 1 • March 2004 In this Issue... New Products pp. 12-14 Functions and Pharmacological Inhibitors of Anti-mTOR: marker for translation initiation Cyclic Nucleotide Phosphodiesterases activation Valeria Vasta and Joe Beavo p. 9 XK469: selective topoisomerase II-β inhibitor he discovery of the cyclic nucleotides 3',5'- p. 10 cyclic monophosphate (cAMP, Prod. No. T ANPs A 9501, A 4137) and guanosine 3',5'-cyclic a Guanylin Y-27632: selective inhibitor STa monophosphate (cGMP, Prod. No. G 7504, NO GTP pGC of Rho associated protein sGC kinase p160ROCK G 6129) led to the first formulation of the second cGMP PDEs NO p. 11 messenger concept. These cyclic nucleotides are 5'GMP now known to be ubiquitous intracellular second SB-431542: potent, messengers that mediate the response of cells to PDEs selective inhibitor of activin a variety of extracellular stimuli through the receptor-like kinase (ALK) activation of cyclic nucleotide-dependent protein PKG receptors kinases, ion channels, GTP-exchange factors and CNG Channels p. 15 their downstream effector systems [1]. The ampli- Protein tude and duration of cAMP and cGMP signals are Phosphorylation SCH-28080: potent Na+, Ca2+ + + controlled by their rates of synthesis by adenylyl inhibitor of gastric H /K - ATPase and guanylyl cyclases, respectively, and their p. 15 degradation by 3’,5'-cyclic nucleotide phospho- a large superfamily of enzymes that hydrolyze the diesterases (PDEs) (Figure 1). PDEs, identified 3' phosphodiester bond in cAMP or cGMP to Peptidomimetic isoform shortly after the discovery of cAMP and cGMP, are form the corresponding 5'-nucleotide selective nNOS inhibitors p. 16 continued on page 3 L-685,458: potent, selective γ-secretase Application Note: inhibitor p. 17 ™ The New Panorama Antibody (Ab) Anti-ILK: marker for integrin-mediated Microarray Cell Signaling Kit: A Unique Tool processes for Protein Expression Analysis p. 18 Eliezer Kopf, Dalia Shnitzer and Dorit Zharhary SB-228357: potent, selective 5-HT2C/2B serotonin receptor Introduction provided valuable information antagonist in many biological areas. p. 18 here is a growing need for However, since there is not technologies that allow Anti-Survivin: marker T always a direct correlation global molecular characteriza- for blocking apoptosis between the mRNA level and tion of biological samples. The p. 19 the expression of the protein, a ability to identify multiple pro- method that can directly assay teins simultaneously has many Compound Libraries proteins is required. Whereas pp. 22-23 applications in basic biological DNA/RNA/oligo arrays give research as well as in disease information on the genetic diagnosis and treatment. The defects that may cause disease, use of DNA arrays for profiling protein microarrays provide mRNA expression in cells has sigma-aldrich.com/cellsignaling continued on page 20 3 Functions and Pharmacological Inhibitors of Cyclic Nucleotide Phosphodiesterases Valeria Vasta and Joe Beavo (continued from cover) monophosphate. This overview focuses on the functions and expressed in multiple isoforms due to different transcription pharmacological inhibitors of mammalian PDEs; for more initiation sites or alternative splicing. A large number of extensive reviews see references [2-4]. transcript variants have been reported in the literature or can be deduced from the EST database, but the physiological significance of this phenomenon is only beginning to be PDE Superfamily elucidated. The PDE families can be differentiated gene- The PDEs are now recognized to form a superfamily of 11 tically, on the basis of sequence homology, and functionally, different, but homologous gene-families that all contain a on the basis of substrate specificity, kinetic properties and conserved catalytic domain of around 300 amino acids near sensitivity to endogenous or pharmacological regulators. The their carboxy terminus [3]. The amino acid sequence identity first functional difference identified between the various in the catalytic domain is usually 35-40% between different PDEs was substrate specificity. Thus, some PDEs hydrolyze families, while it is generally at least 70% between members only cAMP, some hydrolyze only cGMP, while others of the same gene family. Twenty-one residues, in particular, hydrolyze both. Table 1 depicts the 11 gene families, are absolutely conserved across all PDE families and two PDE referred to as PDE1-PDE11, together with their substrate signature motifs (H-N-XX-H\H-D-XX-H) in the active site specificity, tissue localization, their basic mode of regulation appear to form a single pocket, binding two metal ions and some of their selective inhibitors. involved in catalysis [5]. The crystal structures of several PDE catalytic domains have recently been determined [6-9]. The Different PDE isozymes can have specific tissue, cellular and amino terminal region of the PDEs is distinguished by a subcellular distributions and more than one type of PDE is domain and motif organization characteristic of each PDE Cyclic Nucleotide usually present in any given cell. However, the pattern of gene family [3]. This region is involved in subunit and Phosphodiesterases PDE expression can exhibit some degree of variability protein-protein interactions, localization, and allosteric and between different species. The types of PDEs expressed in a covalent modifications affecting catalytic activity. The cell, together with their relative proportions and subcellular nomenclature employed to distinguish each PDE isozyme localization, clearly control the cyclic nucleotide phenotype uses the first two letters to designate the species of origin, of that cell. In addition to literature data on the tissue/cell followed by PDE and the Arabic numeral of the gene family specific expression of the various PDEs, which is not entirely (usually reflecting the order of discovery). The next letter catalogued as yet, information on the expression can be represents the individual gene within the family, followed by obtained from mRNA, ESTs and microarray analysis data- an Arabic numeral identifying the transcript variant. For bases. For example, the sequences (mRNA and ESTs) belong- example, HSPDE8A1 refers to the human PDE8 family, gene ing to each PDE gene family and their tissue of derivation A, transcript variant 1. are listed in a cluster with the name of that PDE in the UniGene database (http://www.ncbi.nlm.nih.gov/entrez/- sigma-aldrich.com/cellsignaling At present, 21 different mammalian PDE genes have been query.fcgi? db=unigene) and in the Geo Microarray analysis identified with each gene generally being highly conserved database (http://www.ncbi.nlm.nih.gov:80/entrez/ between species. In addition, many of the genes are query.fcgi?CMD= search&DB=geo). ANPs Hormone, Neurotransmitter a Guanylin b GPCR NO pGC STa GTP G echnical Service: 1-800-325-5832 sGC S Adenylyl T PDEs NO cGMP 5'-AMP G Cyclase S ATP 5'GMP PDEs cAMP PDEs PKG PKA der: 1-800-325-3010 r CNG Channels Protein Phosphorylation GEFs CNG Channels Protein Phosphorylation Na+, Ca2+ Na+, Ca2+ ol 20, No.1, 2004 O V Figure 1. Cellular pathways of cyclic nucleotide function and regulation. The above schematics show the basic synthetic and regulatory pathways for a) cGMP and b) cAMP metabolism. Various agonists can activate guanylyl cyclases (Panel a) and adenylyl cyclase (Panel b) in different cell types and increase the intracellular levels of cGMP or cAMP, respectively. This ® in turn activates downstream effector systems, such as PKA (protein kinase A), PKG (protein kinase G), cAMP-GEFs (guanine nucleotide exchange factors) and CNG (cyclic nucleotide-gated) channels. By degrading cyclic nucleotides, PDEs control the amplitude, duration and compartmentalization of the cyclic nucleotide signal. Panel a) also illustrates the feedback control of PDE activity by cGMP, ANPs (atrial natriuertic peptides), NO (nitric ® oxide), pGC (particulate guanylyl cyclase), sGC (soluble guanylyl cyclase) and STa (heat-stable enterotoxin). Figure adapted from reference [1]. Celltransmissions 4 Inhibitors of Cyclic Nucleotide Phosphodiesterases...(continued) Table 1 Biochemical and pharmacological characteristics of cyclic nucleotide phosphodiesterase (PDE) isozymes Major Tissue Gene Family Genes Substrate Regulators Inhibitors (Sigma Prod. No.) IC in µM* [Reference] Expression 50 Brain, heart, PDE1A Ca2+-CaM smooth muscle, 8-Methoxymethyl-IBMX (M 2547) 4 [2] PDE1 PDE1B cAMP/cGMP PKA olfactory cilia, Vinpocetine (V 6383) 20 [2] PDE1C CaMKII testis Adrenal cortex, EHNA (E-114) 1 [2] PDE2 PDE2A cGMP/cAMP cGMP brain, heart Trequinsin (T 2057) 0.64-2 [48] Cilostamide (C 7971) 0.005 [2] Cilostazol (C 0737) 0.12 [2] PDE3A Heart, adipose cGMP Enoximone (E 1279) 1 [2] PDE3 PDE3B tissue, pancreas, cAMP>cGMP PKA Imazodan (I 0782) 6 [2] platelets PKB Milrinone (M 4659) 0.30 [2] Trequinsin (T 2057) 0.0003 [2] PDE4A PDE4B PKA Rolipram (R 6520) 2 [2] PDE4 Many tissues cAMP PDE4C PKC YM976 (Y 4877) 0.002 [49] PDE4D Dipyridamole (D 9766) 0.90 [2] DMPPO 0.003 [42] Lung, platelets, Sildenafil (Viagra) 0.004 [50] Cyclic Nucleotide PKA smooth muscle, T-0156 (T 8067) 0.0002 [43] PDE5 PDE5A cGMP PKG Phosphodiesterases corpus T-1032 (T 7692) 0.001 [44] cGMP cavernosum Tadalafil (Cialis) 0.005 [51] Vardenafil (Levitra) 0.0007 [52] Zaprinast (Z 0878) 0.76 [2] Dipyridamole (D 9766) 0.38 [2] PDE6A (α) Rod and cone Transducin Sildenafil 0.074 [51] PDE6 PDE6B (β) photoreceptor cGMP PDE6 γ and δ subunits Tadalafil
Load more

Recommended publications
  • Biomolecules
    CHAPTER 3 Biomolecules 3.1 Carbohydrates In the previous chapter you have learnt about the cell and 3.2 Fatty Acids and its organelles. Each organelle has distinct structure and Lipids therefore performs different function. For example, cell membrane is made up of lipids and proteins. Cell wall is 3.3 Amino Acids made up of carbohydrates. Chromosomes are made up of 3.4 Protein Structure protein and nucleic acid, i.e., DNA and ribosomes are made 3.5 Nucleic Acids up of protein and nucleic acids, i.e., RNA. These ingredients of cellular organelles are also called macromolecules or biomolecules. There are four major types of biomolecules— carbohydrates, proteins, lipids and nucleic acids. Apart from being structural entities of the cell, these biomolecules play important functions in cellular processes. In this chapter you will study the structure and functions of these biomolecules. 3.1 CARBOHYDRATES Carbohydrates are one of the most abundant classes of biomolecules in nature and found widely distributed in all life forms. Chemically, they are aldehyde and ketone derivatives of the polyhydric alcohols. Major role of carbohydrates in living organisms is to function as a primary source of energy. These molecules also serve as energy stores, 2021-22 Chapter 3 Carbohydrade Final 30.018.2018.indd 50 11/14/2019 10:11:16 AM 51 BIOMOLECULES metabolic intermediates, and one of the major components of bacterial and plant cell wall. Also, these are part of DNA and RNA, which you will study later in this chapter. The cell walls of bacteria and plants are made up of polymers of carbohydrates.
    [Show full text]
  • Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences
    molecules Review Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences Yaroslav Staroseletz 1,†, Svetlana Gaponova 1,†, Olga Patutina 1, Elena Bichenkova 2 , Bahareh Amirloo 2, Thomas Heyman 2, Daria Chiglintseva 1 and Marina Zenkova 1,* 1 Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev’s Ave. 8, 630090 Novosibirsk, Russia; [email protected] (Y.S.); [email protected] (S.G.); [email protected] (O.P.); [email protected] (D.C.) 2 School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Rd., Manchester M13 9PT, UK; [email protected] (E.B.); [email protected] (B.A.); [email protected] (T.H.) * Correspondence: [email protected]; Tel.: +7-383-363-51-60 † These authors contributed equally to this work. Abstract: RNA-targeting therapeutics require highly efficient sequence-specific devices capable of RNA irreversible degradation in vivo. The most developed methods of sequence-specific RNA cleav- age, such as siRNA or antisense oligonucleotides (ASO), are currently based on recruitment of either intracellular multi-protein complexes or enzymes, leaving alternative approaches (e.g., ribozymes Citation: Staroseletz, Y.; Gaponova, and DNAzymes) far behind. Recently, site-selective artificial ribonucleases combining the oligonu- S.; Patutina, O.; Bichenkova, E.; cleotide recognition motifs (or their structural
    [Show full text]
  • Cardioactive Agents : Metoprolol, Sotalol and Milrinone. Influence of Myocardial Content and Systolic Interval
    3Õ' î'qt ACUTE HAEMODYNAMIC EFFECTS OF THREE CARDIOACTIVE AGENTS : METOPROLOL, SOTALOL AND MILRINONE. INFLUENCE OF MYOCARDIAL CONTENT AND SYSTOLIC INTERVAL. by Rebecca Helen Ritchie, B.Sc (Hons) A thesis submitted for the degree of Doctor of Philosophy ln The University of Adelaide (Faculty of Medicine) February 1994 Department of Medicine (Cardiology Unit, The Queen Elizabeth Hospital) The University of Adelaide Adelaide, SA, 5000. ll ¡ r -tL',. r,0';(', /1L.)/'t :.: 1 TABLE OF CONTENTS Table of contents 1 Declaration vtl Acknowledgements v111 Publications and communications to learned societies in support of thesis D( Summary xl Chapter 1: General Introduction 1 1.1 Overview 2 1.2 Acute effeots of cardioactive drugs 3 1.2.1 Drug effects 4 l.2.2Determnants of drug effects 5 1.3 Myocardial drug gPtake of cardioactive agents 8 1.3.1 Methods of assessment in humans invívo 9 1.3.2 Results of previous studies 10 1.4Influence of cardioactive drugs on contractile state 11 1.4. 1 Conventional indices 11 I.4.2 The staircase phenomenon t2 1.4.3 The mechanical restitution curve t2 1.5 The present study t4 1.5.1 Current relevant knowledge of the acute haemodynamic effects of the cardioactive drugs under investigation r4 1.5.1.1 Metoprolol 15 1.5.1.2 Sotalol 28 1.5.1.3 Milrinone 43 1.5.2 Cunent relevant knowledge of the short-term pharmacokinetics of the cardioactive drugs under investigation 59 1.5.2.1Metoprolol 59 1.5.2.2 Sotalol 7I ll 1.5.2.3 Milrinone 78 1.5.3 Current relevant knowledge of the potential for rate-dependence of the effects of these
    [Show full text]
  • CASE REPORTS Rhabdomyolysis Following Cardiopulmonary Bypass and Treatment with Enoximone in a Patient Susceptible to Malignant
    Ⅵ CASE REPORTS Anesthesiology 2001; 94:355–7 © 2001 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Rhabdomyolysis following Cardiopulmonary Bypass and Treatment with Enoximone in a Patient Susceptible to Malignant Hyperthermia Friedrich-Christian Riess, M.D.,* Marko Fiege, M.D.,† Sina Moshar, M.D.,‡ Heinz Bergmann, M.D.,§ Niels Bleese, M.D.,ʈ Joachim Kormann, M.D.,# Ralf Weißhorn, M.D.,† Frank Wappler, M.D.†† SEVERE hypercapnia, muscle rigidity, hyperthermia, and After implantation of a mechanical valve (Medtronic Hall; Medtronic, rhabdomyolysis characterize malignant hyperthermia Minneapolis, MN), the ascending aorta was closed and the aortic 1 cross-clamp removed. During reperfusion, the patient exhibited ST (MH) in fulminant form. However, during cardiac opera- Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/94/2/367/402332/0000542-200102000-00029.pdf by guest on 29 September 2021 elevations, with maximal values of 12 mV in all leads. The left ventricle tions using cardiopulmonary bypass (CPB), typical symp- appeared to be ischemic and hypokinetic. A triple bypass was per- toms of MH may not be present. We observed a patient formed using saphenous grafts to the left anterior descending, first undergoing aortic valve replacement, in whom severe post- diagonal branch and the circumflex artery. The patient was then operative rhabdomyolysis and arrhythmias developed after successfully weaned from CPB using a moderate dose of adrenalin (4 ␮ treatment with enoximone during CPB and cardioplegic g/min) and 50 mg enoximone (Perfan; Hoechst, Bad Soden am Ts., Germany). However, toward the completion of the operation, the arrest. Subsequently, in vitro contracture testing showed urine became dark and the minute ventilation necessary to maintain that the patient was susceptible to MH.
    [Show full text]
  • Reprogramming Metabolism by Targeting Sirtuin 6 Attenuates Retinal Degeneration
    The Journal of Clinical Investigation RESEARCH ARTICLE Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration Lijuan Zhang,1,2,3 Jianhai Du,4 Sally Justus,1,2 Chun-Wei Hsu,1,2 Luis Bonet-Ponce,5 Wen-Hsuan Wu,1,2 Yi-Ting Tsai,1,2 Wei-Pu Wu,1,2 Yading Jia,2 Jimmy K. Duong,6 Vinit B. Mahajan,7 Chyuan-Sheng Lin,8 Shuang Wang,6 James B. Hurley,4 and Stephen H. Tsang1,2,9 1The Jonas Children’s Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Department of Ophthalmology, Columbia University, New York, New York, USA. 2Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA. 3Shanxi Eye Hospital, affiliated with Shanxi Medical University, Xinghualing, Taiyuan, China. 4Department of Biochemistry and Ophthalmology, University of Washington, Seattle, Washington, USA. 5Section on Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, NIH, Bethesda, Maryland, USA. 6Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York, New York, USA. 7Omics Lab, University of Iowa, Iowa City, Iowa, USA. 8Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons of Columbia University, New York, New York, USA. 9Departments of Pathology and Cell Biology, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York, USA. Retinitis pigmentosa (RP) encompasses a diverse group of Mendelian disorders leading to progressive degeneration of rods and then cones. For reasons that remain unclear, diseased RP photoreceptors begin to deteriorate, eventually leading to cell death and, consequently, loss of vision.
    [Show full text]
  • Theophylline and Selective PDE Inhibitors As Bronchodilators and Smooth Muscle Relaxants
    Eur Respir J, 1995, 8, 637–642 Copyright ERS Journals Ltd 1995 DOI: 10.1183/09031936.95.08040637 European Respiratory Journal Printed in UK - all rights reserved ISSN 0903 - 1936 SERIES 'THEOPHYLLINE AND PHOSPHODIESTERASE INHIBITORS' Edited by M. Aubier and P.J. Barnes Theophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants K.F. Rabe, H. Magnussen, G. Dent Theophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants. Krankenhaus Grosshansdorf, Zentrum für K.F. Rabe, H. Magnussen, G. Dent. ERS Journals Ltd 1995. Pneumologie und Thoraxchirurgie, LVA ABSTRACT: In addition to its emerging immunomodulatory properties, theophy- Hamburg, Grosshansdorf, Germany. lline is a bronchodilator and also decreases mean pulmonary arterial pressure in vivo. The mechanism of action of this drug remains controversial; adenosine Correspondence: K.F. Rabe Krankenhaus Grosshansdorf antagonism, phosphodiesterase (PDE) inhibition and other actions have been advanced Wöhrendamm 80 to explain its effectiveness in asthma. Cyclic adenosine monophosphate (AMP) and D-22927 Grosshansdorf cyclic guanosine monophosphate (GMP) are involved in the regulation of smooth Germany muscle tone, and the breakdown of these nucleotides is catalysed by multiple PDE isoenzymes. The PDE isoenzymes present in human bronchus and pulmonary artery Keywords: Bronchi have been identified, and the pharmacological actions of inhibitors of these enzy- 3',5'-cyclic-nucleotide phosphodiesterase mes have been investigated. phosphodiesterase inhibitors Human bronchus and pulmonary arteries are relaxed by theophylline and by pulmonary artery selective inhibitors of PDE III, while PDE IV inhibitors also relax precontracted smooth muscle theophylline bronchus and PDE V/I inhibitors relax pulmonary artery. There appears to be some synergy between inhibitors of PDE III and PDE IV in relaxing bronchus, and Received: February 1 1995 a pronounced synergy between PDE III and PDE V inhibitors in relaxing pulmon- Accepted for publication February 1 1995 ary artery.
    [Show full text]
  • Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio della ricerca- Università di Roma La Sapienza Inflammation, Vol. 39, No. 3, June 2016 (# 2016) DOI: 10.1007/s10753-016-0359-6 ORIGINAL ARTICLE Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy Luigi Di Luigi,1 Clarissa Corinaldesi,1 Marta Colletti,1 Sabino Scolletta,2 Cristina Antinozzi,1 Gabriella B. Vannelli,3 Elisa Giannetta,4 Daniele Gianfrilli,4 Andrea M. Isidori,4 Silvia Migliaccio,1 Noemi Poerio,5 Maurizio Fraziano,5 Andrea Lenzi,4 and Clara Crescioli1,6 Abstract—T helper 1 (Th1) type cytokines and chemokines are bioactive mediators in inflammation underling several diseases and co-morbid conditions, such as cardiovascular and metabolic disorders. Th1 chemokine CXCL10 participates in heart damage initiation/progression; cardioprotection has been recently associated with sildenafil, a type 5 phosphodiesterase inhibitor. We aimed to evaluate the effect of sildenafil on CXCL10 in inflammatory conditions associated with diabetic cardiomyopathy. We analyzed: CXCL10 gene and protein in human cardiac, endothelial, and immune cells challenged by pro-inflammatory stimuli with and without sildenafil; serum CXCL10 in diabetic subjects at cardiomy- opathy onset, before and after 3 months of treatment with sildenafil vs. placebo. Sildenafil significantly −7 decreased CXCL10 protein secretion (IC50 =2.6×10 ) and gene expression in human cardiomyocytes and significantly decreased circulating CXCL10 in subjects with chemokine basal level ≥ 930 pg/ml, the cut-off value as assessed by ROC analysis. In conclusion, sildenafil could be a pharmacologic tool to control CXCL10-associated inflammation in diabetic cardiomyopathy.
    [Show full text]
  • PDE4-Inhibitors: a Novel, Targeted Therapy for Obstructive Airways Disease Zuzana Diamant, Domenico Spina
    PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease Zuzana Diamant, Domenico Spina To cite this version: Zuzana Diamant, Domenico Spina. PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease. Pulmonary Pharmacology & Therapeutics, 2011, 24 (4), pp.353. 10.1016/j.pupt.2010.12.011. hal-00753954 HAL Id: hal-00753954 https://hal.archives-ouvertes.fr/hal-00753954 Submitted on 20 Nov 2012 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Accepted Manuscript Title: PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease Authors: Zuzana Diamant, Domenico Spina PII: S1094-5539(11)00006-X DOI: 10.1016/j.pupt.2010.12.011 Reference: YPUPT 1071 To appear in: Pulmonary Pharmacology & Therapeutics Received Date: 2 October 2010 Revised Date: 5 December 2010 Accepted Date: 24 December 2010 Please cite this article as: Diamant Z, Spina D. PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease, Pulmonary Pharmacology & Therapeutics (2011), doi: 10.1016/j.pupt.2010.12.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript.
    [Show full text]
  • The Single Cyclic Nucleotide-Specific Phosphodiesterase of the Intestinal Parasite Giardia Lamblia Represents a Potential Drug Target
    RESEARCH ARTICLE The single cyclic nucleotide-specific phosphodiesterase of the intestinal parasite Giardia lamblia represents a potential drug target Stefan Kunz1,2*, Vreni Balmer1, Geert Jan Sterk2, Michael P. Pollastri3, Rob Leurs2, Norbert MuÈ ller1, Andrew Hemphill1, Cornelia Spycher1¤ a1111111111 1 Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland, 2 Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute of Molecules, Medicines and Systems (AIMMS), Vrije a1111111111 Universiteit Amsterdam, Amsterdam, The Netherlands, 3 Department of Chemistry and Chemical Biology, a1111111111 Northeastern University, Boston, Massachusetts, United States of America a1111111111 a1111111111 ¤ Current address: Euresearch, Head Office Bern, Bern, Switzerland * [email protected] Abstract OPEN ACCESS Citation: Kunz S, Balmer V, Sterk GJ, Pollastri MP, Leurs R, MuÈller N, et al. (2017) The single cyclic Background nucleotide-specific phosphodiesterase of the Giardiasis is an intestinal infection correlated with poverty and poor drinking water quality, intestinal parasite Giardia lamblia represents a potential drug target. PLoS Negl Trop Dis 11(9): and treatment options are limited. According to the Center for Disease Control and Preven- e0005891. https://doi.org/10.1371/journal. tion, Giardia infections afflict nearly 33% of people in developing countries, and 2% of the pntd.0005891 adult population in the developed world. This study describes the single cyclic nucleotide- Editor: Aaron R. Jex, University of Melbourne, specific phosphodiesterase (PDE) of G. lamblia and assesses PDE inhibitors as a new gen- AUSTRALIA eration of anti-giardial drugs. Received: December 5, 2016 Accepted: August 21, 2017 Methods Published: September 15, 2017 An extensive search of the Giardia genome database identified a single gene coding for a class I PDE, GlPDE.
    [Show full text]
  • Signal Transduction Guide
    Signal Transduction Product Guide | 2007 NEW! Selective T-type Ca2+ channel blockers, NNC 55-0396 and Mibefradil ZM 447439 – Novel Aurora Kinase Inhibitor NEW! Antibodies for Cancer Research EGFR-Kinase Selective Inhibitors – BIBX 1382 and BIBU 1361 DRIVING RESEARCH FURTHER Calcium Signaling Agents ...................................2 G Protein Reagents ...........................................12 Cell Cycle and Apoptosis Reagents .....................3 Ion Channel Modulators ...................................13 Cyclic Nucleotide Related Tools ...........................7 Lipid Signaling Agents ......................................17 Cytokine Signaling Agents ..................................9 Nitric Oxide Tools .............................................19 Enzyme Inhibitors/Substrates/Activators ..............9 Protein Kinase Reagents....................................22 Glycobiology Agents .........................................12 Protein Phosphatase Reagents ..........................33 Neurochemicals | Signal Transduction Agents | Peptides | Biochemicals Signal Transduction Product Guide Calcium Signaling Agents ......................................................................................................................2 Calcium Binding Protein Modulators ...................................................................................................2 Calcium ATPase Modulators .................................................................................................................2 Calcium Sensitive Protease
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Impedes Transport of GRK1 and PDE6 Catalytic Subunits to Photoreceptor Outer Segments
    Deletion of PrBP/␦ impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segments H. Zhang*, S. Li*, T. Doan†, F. Rieke†‡, P. B. Detwiler†, J. M. Frederick*, and W. Baehr*§¶ʈ *John A. Moran Eye Center, University of Utah Health Science Center, Salt Lake City, UT 84132; †Department of Physiology and Biophysics and ‡Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195; and Departments of §Neurobiology and Anatomy and ¶Biology, University of Utah, Salt Lake City, UT 84112 Edited by Jeremy Nathans, Johns Hopkins University School of Medicine, Baltimore, MD, and approved April 11, 2007 (received for review February 23, 2007) The mouse Pde6d gene encodes a ubiquitous prenyl binding chains (5, 7). Posttranslational sorting and targeting of proteins protein, termed PrBP/␦, of largely unknown physiological function. occurs in all cells and is of particular importance in photore- PrBP/␦ was originally identified as a putative rod cGMP phospho- ceptors, which renew their entire outer segments roughly every diesterase (PDE6) subunit in the retina, where it is relatively 10 days (8). Because of compartmentalization of inner and outer abundant. To investigate the consequences of Pde6d deletion in segments and very active metabolism, photoreceptors are re- .retina, we generated a Pde6d؊/؊ mouse by targeted recombina- garded as model cells to study protein trafficking tion. Although manifesting reduced body weight, the Pde6d؊/؊ PrBP/␦, originally thought to be a subunit of PDE6 and termed mouse was viable and fertile and its retina developed normally. PDE␦ (9), was shown recently to be a prenyl binding protein (10, Immunocytochemistry showed that farnesylated rhodopsin kinase 11) and subsequently named PrBP/␦ to reflect this fact (12).
    [Show full text]