DOCSLIB.ORG

1 Pharmacological Characterization of AZD5069, a Slowly Reversible CXCR2 Antagonist Table S1. Kinase Panel Screening Performe

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
1 Pharmacological Characterization of AZD5069, a Slowly Reversible CXCR2 Antagonist Table S1. Kinase Panel Screening Performe Pharmacological Characterization of AZD5069, a Slowly Reversible CXCR2 Antagonist Nicholls DJ, Wiley K, Dainty I, MacIntosh F, Phillips C, Gaw A, Kärrman Mårdh C. JPET #221358 Pharmacological Characterization of AZD5069, a Slowly Reversible CXCR2 Antagonist David Nicholls, Katherine Wiley, Ian Dainty, Fraser MacIntosh, Caroline Phillips, Alasdair Gaw, Carina Kärrman Mårdh. The Journal of Pharmacology and Experimental Therapeutics Table S1. Kinase panel screening performed at Dundee University ATP Inhibition Target (μM) (%) AMP-activated Protein Kinase 50 19 Cyclin Dependent Kinase 2:Cyclin A 20 18 Checkpoint Kinase I 20 10 Casein Kinase 1 20 -6 Casein Kinase 2 5 4 Lymphocyte-Specific Protein Tyrosine Kinase 50 -5 Mitogen Activated Protein Kinase 1 50 13 MAPK Activated Protein Kinase-1a 50 -3 MAPK Activated Protein Kinase-2 20 13 Mitogen Activated Protein Kinase Kinase 1 5 21 Protein Kinase, cAMP-dependent, catalytic, alpha 5 -71 v-akt murine thymoma viral oncogene homolog 1 5 19 Protein Kinase C alpha 20 9 p38 Regulated Activated Kinase 20 7 Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A 50 15 Glycogen Synthase Kinase-3 beta 5 12 Mitogen Activated Protein Kinase 8 20 9 Mitogen and Stress Activated Protein Kinase 1 20 8 P70S6 Kinase 20 22 Phospho B Kinase 20 4 3-Phosphoinositide Dependent Protein Kinase-1 20 10 Rho Associated, Coiled Coil Containing Protein Kinase 2 20 2 Stress Activated Protein Kinase 2a 50 4 Stress Activated Protein Kinase 2b 20 17 Serum and Glucocorticoid Regulated Kinase? 20 11 1 Pharmacological Characterization of AZD5069, a Slowly Reversible CXCR2 Antagonist Nicholls DJ, Wiley K, Dainty I, MacIntosh F, Phillips C, Gaw A, Kärrman Mårdh C. JPET #221358 Table S2. Secondary pharmacology screening performed at MDS Pharma Conc Inhibition Cat# Target (μM) (%) 138000 15 Lipoxygenase 10 -7 136010 5 Lipoxygenase 10 -4 271110 5-Hydroxytryptamine Receptor 1A 10 -15 271200 5-Hydroxytryptamine Receptor 1B 10 -5 271650 5-Hydroxytryptamine Receptor 2A 10 2 271700 5-Hydroxytryptamine Receptor 2B 10 5 271800 5-Hydroxytryptamine Receptor 2C 10 -7 271910 5-Hydroxytryptamine Receptor 3A 10 -12 272000 5-Hydroxytryptamine Receptor 4 10 -4 272100 5-Hydroxytryptamine Receptor 5A 10 14 272200 5-Hydroxytryptamine Receptor 5B 10 -1 104010 Acetylcholinesterase 10 9 200510 Adenosine Receptor A1 10 -4 200610 Adenosine Receptor A2a 10 -4 200720 Adenosine Receptor A3 10 5 202000 Adenosine Transporter 10 -2 203100 Adrenergic Receptor Alpha 1A 10 21 203200 Adrenergic Receptor Alpha 1B 10 -5 203400 Adrenergic Receptor Alpha 1D 10 10 203620 Adrenergic Receptor Alpha 2A 10 7 203710 Adrenergic Receptor Alpha 2B 10 -7 203800 Adrenergic Receptor Alpha 2C 10 2 204010 Adrenergic Receptor Beta 1 10 1 204110 Adrenergic Receptor Beta 2 10 -4 204200 Adrenergic Receptor Beta 3 10 6 107000 Aldose Reductase 10 75 232600 AMPA/Kainate Receptor 10 12 285010 Androgen Receptor 10 6 107300 Angiotensin Converting Enzyme 10 0 210020 Angiotensin II Receptor AT1 10 3 210110 Angiotensin II Receptor AT2 10 5 265600 ATP-sensitive Potasium Channel 10 3 211600 Bombesin Receptor BRS-1 30 3 211700 Bombesin Receptor BRS-2 30 2 212510 Bradykinin Receptor 1 10 8 212610 Bradykinin Receptor 2 30 -5 213610 Calcitonin Receptor 30 8 216000 Calcium channel 30 4 214600 Calcium channel 10 7 214510 Calcium channel 10 3 215000 Calcium channel 10 -5 2 Pharmacological Characterization of AZD5069, a Slowly Reversible CXCR2 Antagonist Nicholls DJ, Wiley K, Dainty I, MacIntosh F, Phillips C, Gaw A, Kärrman Mårdh C. JPET #221358 108010 Calpain 10 5 217020 Cannabinoid Receptor 1 30 -3 217100 Cannabinoid Receptor 2 30 -9 112000 Carbonic Anhydrase 10 31 112020 Carbonic Anhydrase 10 2 163000 Caspase 1 10 -1 163200 Caspase 3 10 -1 163280 Caspase 5 10 -14 163300 Caspase 6 10 0 112250 Cathepsin B 10 -19 112510 Cathepsin G 10 4 217500 CCR1 30 4 217550 CCR2 30 73 217650 CCR4 30 -2 217700 CCR5 30 58 214010 CGRP Receptor 10 -7 218010 Cholecystokinin A Receptor 30 -1 218120 Cholecystokinin B Receptor 30 13 219000 Choline Transporter 10 7 113400 Chymotrypsin 10 4 219150 Corticotropin releasing hormone receptor 1 10 3 219500 Dopamine Receptor D1 10 -2 219600 Dopamine Receptor D2 10 6 219700 Dopamine Receptor D2 10 -13 219800 Dopamine Receptor D3 10 -1 219900 Dopamine Receptor D4 10 1 220000 Dopamine Receptor D4 10 3 220100 Dopamine Receptor D4 10 -1 220200 Dopamine Receptor D5 10 -3 220320 Dopamine Transporter 10 2 163950 Endothelin Converting Enzyme 1 10 20 224010 Endothelin Receptor A 10 7 224110 Endothelin Receptor B 30 9 143000 eNOS 10 5 170010 Epidermal Growth Factor Receptor 10 11 171790 Fibroblast Growth Factor Receptor 1 10 -4 172010 FYN oncogene related to SRC 10 1 226500 GABA Receptor 10 7 226600 GABA Receptor 10 8 228700 GABAB Receptor 10 7 228600 GABAB Receptor 10 -3 231510 Galanin Receptor 1 30 2 231600 Galanin Receptor 2 30 3 239300 Ghrelin Receptor 30 10 231700 Glucagon Like Peptide 1 Receptor 30 2 3 Pharmacological Characterization of AZD5069, a Slowly Reversible CXCR2 Antagonist Nicholls DJ, Wiley K, Dainty I, MacIntosh F, Phillips C, Gaw A, Kärrman Mårdh C. JPET #221358 232010 Glucocorticoid Receptor 10 4 239000 Glycine receptor 10 -9 239100 Glycine 10 27 239610 Histamine Receptor H1 10 1 239710 Histamine Receptor H2 10 -3 239810 Histamine Receptor H3 10 14 239900 Histamine Receptor H4 10 -20 241000 Imidazoline I2 10 3 144000 iNOS 10 -7 175000 Insulin Receptor 10 16 243000 Insulin Receptor 10 7 232700 Kainate GLU Receptor 10 -6 286900 Kinase Insert Domain Receptor 30 0 250400 Leptin Receptor 10 10 250510 Leukotriene B4 Receptor 10 -9 250460 Leukotriene Receptor CysT1 10 8 115400 Matrix Metalloproteinase 14 10 -7 114210 Matrix Metalloproteinase 2 10 -5 251100 Melanocortin Receptor 1 30 -7 251300 Melanocortin Receptor 3 30 11 251350 Melanocortin Receptor 4 30 3 251400 Melanocortin Receptor 5 30 9 251600 Melatonin Receptor 1 30 6 251500 Melatonin Receptor 10 2 175030 Met proto-oncogene (hepatocyte growth factor receptor) 10 7 176700 Mitogen-Activated Protein Kinase 12 10 6 140010 Monoamine Oxidase A 10 0 252200 Motilin Receptor 30 -1 252600 Muscarinic Acetylcholine Receptor 1 10 -9 252700 Muscarinic Acetylcholine Receptor 2 10 -6 252800 Muscarinic Acetylcholine Receptor 3 10 -7 252900 Muscarinic Acetylcholine Receptor 4 10 2 253000 Muscarinic Acetylcholine Receptor 5 10 -2 254500 Muscarinic Acetylcholine Receptor 10 4 121000 Myeloperoxidase 10 16 107700 Na+/K+ transporting ATPase 10 4 211000 Natriuretic Peptide Receptor 30 7 255510 Neurokinin Receptor 1 10 6 255600 Neurokinin Receptor 2 10 0 255710 Neurokinin Receptor 3 10 11 257010 Neuropeptide Y Receptor 1 30 5 257110 Neuropeptide Y Receptor 2 10 -5 258010 Neurotensin Receptor 1 10 3 258590 Nicotinic Acetylcholine Receptor 10 -9 232810 NMDA Receptor 10 22 4 Pharmacological Characterization of AZD5069, a Slowly Reversible CXCR2 Antagonist Nicholls DJ, Wiley K, Dainty I, MacIntosh F, Phillips C, Gaw A, Kärrman Mårdh C. JPET #221358 233000 NMDA Receptor 10 -2 234000 NMDA Receptor 10 5 232910 NMDA Receptor 10 -13 142000 nNOS 10 0 260600 Nociceptin Receptor OPRL1 10 3 204410 Norepinephrine Transporter 10 -1 226010 Oestrogen Receptor Alpha 10 7 226050 Oestrogen Receptor Beta 10 -5 260110 Opioid Receptor Delta 1 10 -4 260210 Opioid Receptor Kappa 1 10 -9 260410 Opioid Receptor Mu 1 10 -8 160000 Pancreatic Phospholipase A2 10 8 152000 Phosphodiesterase 3 10 3 270000 Phosphodiesterase 4 10 5 154000 Phosphodiesterase 4 10 7 156000 Phosphodiesterase 5 10 13 156100 Phosphodiesterase 6 10 5 265010 Platelet Activating Factor Receptor 30 -1 265200 Platelet Derived Growth Factor Receptor 30 -1 265500 Potassium Channel 30 -18 265800 Potassium Channel 10 -2 268020 Progesterone receptor 10 1 268410 Prostaglandin Receptor EP4 10 5 116020 Prostaglandin-endoperoxide synthase 1 10 4 118010 Prostaglandin-endoperoxide synthase 2 10 10 190010 Protein Tyrosine Phosphatase 10 10 268810 Purine G Protein-coupled Receptor 10 13 268700 Purine receptor 10 3 164600 Renin 10 9 269500 Retinoid X Receptor 10 5 171520 Rho Associated 10 -3 274020 Serotonin Transporter 10 4 274030 Serotonin Transporter 10 -3 278110 Sigma1 10 2 278200 Sigma2 10 3 279510 Sodium Channel 10 4 282510 Somatostatin Receptor 1 30 3 282700 Somatostatin Receptor 2 10 -2 282530 Somatostatin Receptor 3 30 3 282900 Somatostatin Receptor 4 10 -3 283000 Somatostatin Receptor 5 10 10 165000 Thrombin 10 2 285510 Thromboxane Receptor A2 10 -8 286000 Thyrotropin Releasing Hormone Receptor 1 10 9 286810 Transient Receptor Potential Cation Channel V 10 -6 5 Pharmacological Characterization of AZD5069, a Slowly Reversible CXCR2 Antagonist Nicholls DJ, Wiley K, Dainty I, MacIntosh F, Phillips C, Gaw A, Kärrman Mårdh C. JPET #221358 226700 Translocator Protein (18kDa) 10 18 226400 Undefined 10 13 171800 Vascular Endothelial Growth Factor Receptor 1 10 12 287520 Vasopressin Receptor 1A 10 0 287560 Vasopressin Receptor 1B 10 6 287610 Vasopressin Receptor 2 10 9 252010 Vesicular Monoamine Transporter 10 34 287010 VPAC Receptor 1 30 -2 176800 v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog 10 -1 175080 v-yes-1 Yamaguchi Sarcoma Viral Oncogene Homolog 1 10 -1 6 .
Load more

Recommended publications
  • Strategies to Increase ß-Cell Mass Expansion
    This electronic thesis or dissertation has been downloaded from the King’s Research Portal at https://kclpure.kcl.ac.uk/portal/ Strategies to increase -cell mass expansion Drynda, Robert Lech Awarding institution: King's College London The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without proper acknowledgement. END USER LICENCE AGREEMENT Unless another licence is stated on the immediately following page this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence. https://creativecommons.org/licenses/by-nc-nd/4.0/ You are free to copy, distribute and transmit the work Under the following conditions: Attribution: You must attribute the work in the manner specified by the author (but not in any way that suggests that they endorse you or your use of the work). Non Commercial: You may not use this work for commercial purposes. No Derivative Works - You may not alter, transform, or build upon this work. Any of these conditions can be waived if you receive permission from the author. Your fair dealings and other rights are in no way affected by the above. Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 Strategies to increase β-cell mass expansion A thesis submitted by Robert Drynda For the degree of Doctor of Philosophy from King’s College London Diabetes Research Group Division of Diabetes & Nutritional Sciences Faculty of Life Sciences & Medicine King’s College London 2017 Table of contents Table of contents .................................................................................................
    [Show full text]
  • The Evolutionary Origin of the Vasopressin/V2-Type Receptor/ Aquaporin Axis and the Urine-Concentrating Mechanism
    Endocrine (2012) 42:63–68 DOI 10.1007/s12020-012-9634-y MINI REVIEW The evolutionary origin of the vasopressin/V2-type receptor/ aquaporin axis and the urine-concentrating mechanism Kristian Vinter Juul Received: 5 December 2011 / Accepted: 8 February 2012 / Published online: 29 February 2012 Ó Springer Science+Business Media, LLC 2012 Abstract In this mini-review, current evidence for how circadian regulation of urine volume and osmolality that the vasopressin/V2-type receptor/aquaporin axis developed may lead to enuresis and nocturia. co-evolutionary as a crucial part of the urine-concentrating mechanism will be presented. The present-day human Keywords Arginine vasopressin Á V2-R Á AQPs Á kidney, allowing the concentration of urine up to a maxi- Evolution mal osmolality around 1200 mosmol kg-1—or urine to plasma osmolality ratio around 4—with essentially no sodium secreted is the result of up to 3 billion years evo- Introduction lution. Moving from aquatic to terrestrial habitats required profound changes in kidney morphology, most notable the The evolutionary process that ultimately lead to the loops of Henle modifying the kidneys from basically a development of the urine-concentrating mechanism was water excretory system to a water conserving system. originally proposed by Homer Smith, the ‘Father of Renal Vasopressin-like molecules has during the evolution played Physiology’ [1], and is now generally accepted: First cru- a significant role in body fluid homeostasis, more specifi- cial step was salt water vertebrates’ simple nephron cally, the osmolality of body liquids by controlling the developing into nephrons with large glomerular capillaries elimination/reabsorption of fluid trough stimulating and proximal and distal tubules in fresh water vertebrates, V2-type receptors to mobilize aquaporin water channels in allowing the excretion of the vast amounts of excess water the renal collector tubules.
    [Show full text]
  • Receptor-Arrestin Interactions: the GPCR Perspective
    biomolecules Review Receptor-Arrestin Interactions: The GPCR Perspective Mohammad Seyedabadi 1,2 , Mehdi Gharghabi 3, Eugenia V. Gurevich 4 and Vsevolod V. Gurevich 4,* 1 Department of Toxicology & Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari 48471-93698, Iran; [email protected] 2 Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari 48167-75952, Iran 3 Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; [email protected] 4 Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-615-322-7070; Fax: +1-615-343-6532 Abstract: Arrestins are a small family of four proteins in most vertebrates that bind hundreds of different G protein-coupled receptors (GPCRs). Arrestin binding to a GPCR has at least three functions: precluding further receptor coupling to G proteins, facilitating receptor internalization, and initiating distinct arrestin-mediated signaling. The molecular mechanism of arrestin–GPCR interactions has been extensively studied and discussed from the “arrestin perspective”, focusing on the roles of arrestin elements in receptor binding. Here, we discuss this phenomenon from the “receptor perspective”, focusing on the receptor elements involved in arrestin binding and empha- sizing existing gaps in our knowledge that need to be filled. It is vitally important to understand the role of receptor elements in arrestin activation and how the interaction of each of these elements with arrestin contributes to the latter’s transition to the high-affinity binding state. A more precise knowledge of the molecular mechanisms of arrestin activation is needed to enable the construction of arrestin mutants with desired functional characteristics.
    [Show full text]
  • Homogeneous Time-Resolved Fluorescence-Based Assay To
    Homogeneous time-resolved fluorescence-based assay to monitor extracellular signal-regulated kinase signaling in a high-throughput format Mohammed Akli Ayoub, Julien Trebaux, Julie Vallaghe, Fabienne Charrier-Savournin, Khaled Al-Hosaini, Arturo Gonzalez Moya, Jean-Philippe Pin, Kevin D. Pfleger, Eric Trinquet To cite this version: Mohammed Akli Ayoub, Julien Trebaux, Julie Vallaghe, Fabienne Charrier-Savournin, Khaled Al- Hosaini, et al.. Homogeneous time-resolved fluorescence-based assay to monitor extracellular signal- regulated kinase signaling in a high-throughput format. Frontiers in Endocrinology, Frontiers, 2014, 5, pp.94. 10.3389/fendo.2014.00094. hal-01943335 HAL Id: hal-01943335 https://hal.archives-ouvertes.fr/hal-01943335 Submitted on 3 Dec 2018 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. METHODS ARTICLE published: 23 June 2014 doi: 10.3389/fendo.2014.00094 Homogeneous time-resolved fluorescence-based assay to monitor extracellular signal-regulated kinase signaling in a high-throughput format Mohammed Akli Ayoub1*, JulienTrebaux 2,
    [Show full text]
  • Effects of Chronic Psychosocial Stress on HPA Axis Functionality in Male C57BL/6 Mice and the Impact of Trait Anxiety on the Individual Stress Vulnerability
    Effects of chronic psychosocial stress on HPA axis functionality in male C57BL/6 mice and the impact of trait anxiety on the individual stress vulnerability DISSERTATION ZUR ERLANGUNG DES DOKTORGRADES DER NATURWISSENSCHAFTEN (DR. RER. NAT.) DER FAKULTÄT FÜR BIOLOGIE UND VORKLINISCHE MEDIZIN DER UNIVERSITÄT REGENSBURG vorgelegt von Andrea Monika Füchsl aus Straubing im Jahr 2013 Das Promotionsgesuch wurde eingereicht am: 04.10.2013 Die Arbeit wurde angeleitet von: Prof. Dr. rer. nat. Inga D. Neumann Unterschrift: DISSERTATION Durchgeführt am Institut für Zoologie der Universität Regensburg TABLE OF CONTENTS I Table of Contents Chapter 1 – Introduction 1 Stress ...................................................................................................... 1 1.1 The Stress System ..................................................................................... 1 1.1.2 Sympathetic nervous system (SNS) ..................................................... 2 1.2.2 Hypothalamic-Pituitary-Adrenal (HPA) axis .......................................... 4 1.2 Acute vs. chronic/repeated stress ............................................................. 13 1.3 Psychosocial stress .................................................................................. 18 2 GC Signalling ....................................................................................... 20 2.1 Corticosteroid availability .......................................................................... 20 2.2 Corticosteroid receptor types in the brain .................................................
    [Show full text]
  • Download the Poster
    Real-Time Kinetic Analysis of GPCR Signaling in Stable PathHunter® Cell Lines Paul Tewson (Montana Molecular), Sam Hoare (Pharmechanics), Thom Hughes (Montana Molecular), Anne Marie Quinn (Montana Molecular), Paul Shapiro (Eurofins DiscoverX), Nurulain T. Zaveri (Astraea Therapeutics) Overview Investigate GPCR biology with a simple protocol that Kinetic measurements make it possible to extract combines DiscoverX cells and Montana Molecular the initial rate parameter (kTau), which can be used • Eurofins DiscoverX stable cell lines are widely used biosensors to quantify agonist activity at GPCRs such as the tools in GPCR drug discovery, providing endpoint DAY 1 TRANSDUCE AND PLATE CELLS Nociceptin Opioid receptor (OPRL1) assays for G-protein signaling, GPCR internalization, STEP 1 The green cADDis Sensor 20 and β-arrestin recruitment. Prepare cells NOFQ 1. µM can be used in DiscoverX cells 10 nM expressing the Nociceptin 1.8 Opioid receptor to detect • Montana Molecular offers genetically-fluorescent 10 M 2+ + + Gi signaling. Dose response biosensors to detect cAMP, DAG, PIP2 , Ca , c GMP, STEP 2 BacMam Media HDAC 1.6 3.2 nM measurements to the agonist β-arrestin, and cell stress. Prepare viral transduction reaction Inhibitor Transduction Mix 1 nM nociceptin/orphanin FQ were 1.4 made, and the kinetic data was 0.2 nM used use determine the EC50 • The fluorescent sensors can be used effectively in both 0. nM by calculating the initial rate STEP 3 1.2 PathHunter® and cAMP Hunter® CHO-K1 cell lines to 0.032 M of activity (kTau) at each dose. Mix cells and transduction reaction + The initial rate of signaling 1.0 monitor signaling kinetics of G-protein and β-arrestin 0.01 nM (kTau) is a direct measure of pathways in live cells, in real time.
    [Show full text]
  • Biased Signaling of G Protein Coupled Receptors (Gpcrs): Molecular Determinants of GPCR/Transducer Selectivity and Therapeutic Potential
    Pharmacology & Therapeutics 200 (2019) 148–178 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Biased signaling of G protein coupled receptors (GPCRs): Molecular determinants of GPCR/transducer selectivity and therapeutic potential Mohammad Seyedabadi a,b, Mohammad Hossein Ghahremani c, Paul R. Albert d,⁎ a Department of Pharmacology, School of Medicine, Bushehr University of Medical Sciences, Iran b Education Development Center, Bushehr University of Medical Sciences, Iran c Department of Toxicology–Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Iran d Ottawa Hospital Research Institute, Neuroscience, University of Ottawa, Canada article info abstract Available online 8 May 2019 G protein coupled receptors (GPCRs) convey signals across membranes via interaction with G proteins. Origi- nally, an individual GPCR was thought to signal through one G protein family, comprising cognate G proteins Keywords: that mediate canonical receptor signaling. However, several deviations from canonical signaling pathways for GPCR GPCRs have been described. It is now clear that GPCRs can engage with multiple G proteins and the line between Gprotein cognate and non-cognate signaling is increasingly blurred. Furthermore, GPCRs couple to non-G protein trans- β-arrestin ducers, including β-arrestins or other scaffold proteins, to initiate additional signaling cascades. Selectivity Biased Signaling Receptor/transducer selectivity is dictated by agonist-induced receptor conformations as well as by collateral fac- Therapeutic Potential tors. In particular, ligands stabilize distinct receptor conformations to preferentially activate certain pathways, designated ‘biased signaling’. In this regard, receptor sequence alignment and mutagenesis have helped to iden- tify key receptor domains for receptor/transducer specificity.
    [Show full text]
  • Supplementary Table 2
    Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942
    [Show full text]
  • Pflugers Final
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Serveur académique lausannois A comprehensive analysis of gene expression profiles in distal parts of the mouse renal tubule. Sylvain Pradervand2, Annie Mercier Zuber1, Gabriel Centeno1, Olivier Bonny1,3,4 and Dmitri Firsov1,4 1 - Department of Pharmacology and Toxicology, University of Lausanne, 1005 Lausanne, Switzerland 2 - DNA Array Facility, University of Lausanne, 1015 Lausanne, Switzerland 3 - Service of Nephrology, Lausanne University Hospital, 1005 Lausanne, Switzerland 4 – these two authors have equally contributed to the study to whom correspondence should be addressed: Dmitri FIRSOV Department of Pharmacology and Toxicology, University of Lausanne, 27 rue du Bugnon, 1005 Lausanne, Switzerland Phone: ++ 41-216925406 Fax: ++ 41-216925355 e-mail: [email protected] and Olivier BONNY Department of Pharmacology and Toxicology, University of Lausanne, 27 rue du Bugnon, 1005 Lausanne, Switzerland Phone: ++ 41-216925417 Fax: ++ 41-216925355 e-mail: [email protected] 1 Abstract The distal parts of the renal tubule play a critical role in maintaining homeostasis of extracellular fluids. In this review, we present an in-depth analysis of microarray-based gene expression profiles available for microdissected mouse distal nephron segments, i.e., the distal convoluted tubule (DCT) and the connecting tubule (CNT), and for the cortical portion of the collecting duct (CCD) (Zuber et al., 2009). Classification of expressed transcripts in 14 major functional gene categories demonstrated that all principal proteins involved in maintaining of salt and water balance are represented by highly abundant transcripts. However, a significant number of transcripts belonging, for instance, to categories of G protein-coupled receptors (GPCR) or serine-threonine kinases exhibit high expression levels but remain unassigned to a specific renal function.
    [Show full text]
  • A Novel Mutation in the Avpr2gene Causing Congenital Nephrogenic
    ORI GI NAL AR TIC LE DO I: 10.4274/jcrpe.0097 J Clin Res Pediatr Endocrinol 2018;10(4):350-356 A Novel Mutation in the AVPR2 Gene Causing Congenital Nephrogenic Diabetes Insipidus Aslı Çelebi Tayfur1*, Tuğçe Karaduman2*, Merve Özcan Türkmen2, Dilara Şahin2, Aysun Çaltık Yılmaz1, Bahar Büyükkaragöz1, Ayşe Derya Buluş3, Hatice Mergen2 1Keçiören Training and Research Hospital, Clinic of Pediatric Nephrology, Ankara, Turkey 2Hacettepe University Faculty of Science, Department of Biology, Ankara, Turkey 3Keçiören Training and Research Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey *These authors contributed equally to this work. What is already known on this topic? About 90 percent of all cases of hereditary nephrogenic diabetes insipidus result from mutations in the AVPR2 gene. To date, more than 250 mutations have been identified comprising missense, nonsense, small insertions and deletions, large deletions and complex rearrangements in AVPR2 gene. What this study adds? In this study, we found a novel hemizygous missense mutation in the AVPR2 gene at the position 80th in exon 2 causing congenital nephrogenic diabetes insipidus in a 6-year-old boy presenting with growth failure and dull normal cognitive functions. Abstract Objective: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by a renal insensitivity to arginine vasopressin (AVP). In the majority of the cases, CNDI is caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. Our objective is to report a novel mutation in the AVPR2 gene causing CNDI in a 6-year-old boy, presenting with growth failure and dull normal cognitive functions. Methods: The proband was the third off-spring of non-consanguineous parents and had polyuria (4.3 L/day), polydipsia (5 L/day).
    [Show full text]
  • Vasopressin and Oxytocin in Control of the Cardiovascular System
    Send Orders of Reprints at [email protected] 218 Current Neuropharmacology, 2013, 11, 218-230 Vasopressin and Oxytocin in Control of the Cardiovascular System Nina Japundi-igon* Professor of Basic and Clinical Pharmacology and Toxicology, University of Belgrade School of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology, Dr Subotica 1, Belgrade, Republic of Serbia Abstract: Vasopressin (VP) and oxytocin (OT) are mainly synthesized in the magnocellular neurons of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. Axons from the magnocellular part of the PVN and SON project to neurohypophysis where VP and OT are released in blood to act like hormones. Axons from the parvocellular part of PVN project to extra-hypothalamic brain areas (median eminence, limbic system, brainstem and spinal cord) where VP and OT act like neurotransmitters/modulators. VP and OT act in complementary manner in cardiovascular control, both as hormones and neurotransmitters. While VP conserves water and increases circulating blood volume, OT eliminates sodium. Hyperactivity of VP neurons and quiescence of OT neurons in PVN underlie osmotic adjustment to pregnancy. In most vascular beds VP is a potent vasoconstrictor, more potent than OT, except in the umbilical artery at term. The vasoconstriction by VP and OT is mediated via V1aR. In some vascular beds, i.e. the lungs and the brain, VP and OT produce NO dependent vasodilatation. Peripherally, VP has been found to enhance the sensitivity of the baro-receptor while centrally, VP and OT increase sympathetic outflow, suppresse baro-receptor reflex and enhance respiration. Whilst VP is an important mediator of stress that triggers ACTH release, OT exhibits anti-stress properties.
    [Show full text]
  • Federal Register/Vol. 83, No. 121/Friday, June 22, 2018/Notices
    Federal Register / Vol. 83, No. 121 / Friday, June 22, 2018 / Notices 29127 Enhancement Award; 93.936, NIH Acquired (HHS Reference No. E–619–2013–0–US– within fifteen (15) days from the date of Immunodeficiency Syndrome Research Loan 01); this published notice, the National Repayment Program; 93.187, Undergraduate 2. PCT Application No. PCT/US2014/ Institute of Dental and Craniofacial Scholarship Program for Individuals from 058613, filed October 1, 2014 and Research receives written evidence and Disadvantaged Backgrounds, National entitled ‘‘Methods of Modulating Institutes of Health, HHS) argument that establishes that the grant Erythropoiesis with Arginine of the license would not be consistent Dated: June 19, 2018. Vasopressin Receptor 1B Molecules’’ with the requirements of 35 U.S.C. 209 Natasha M. Copeland, (HHS Reference No. E–619–2013–0– and 37 CFR part 404. PCT–02); In response to this Notice, the public Program Analyst, Office of Federal Advisory 3. U.S. Patent Application No. 15/ Committee Policy. may file comments or objections. 022,531, filed March 16, 2016 and [FR Doc. 2018–13419 Filed 6–21–18; 8:45 am] Comments and objections, other than entitled ‘‘Methods of Modulating those in the form of a license BILLING CODE 4140–01–P Erythropoiesis with Arginine application, will not be treated Vasopressin Receptor 1B Molecules’’ confidentially, and may be made (HHS Reference No. E–619–2013–0–US– DEPARTMENT OF HEALTH AND publicly available. 03); HUMAN SERVICES License applications submitted in The patent rights in these inventions response to this Notice will be National Institutes of Health have been assigned and/or exclusively presumed to contain business licensed to the government of the confidential information and any release Prospective Grant of an Exclusive United States of America.
    [Show full text]