DOCSLIB.ORG

Enhancement of Sodium Excretion by Substance P During Saline Loading in the Canine Puppy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Enhancement of Sodium Excretion by Substance P During Saline Loading in the Canine Puppy SODIUM EXCRETION 737 14. Hodgkinson. A.: Biochemical aspects of primary hyperparathyroidism: an anal- glucose. sodium and water by the normal human jejunum. Clin. Sci., 36: 119 ysis of 50 cases. Clin. Sci., 25: 231 (1963). (1%9). 15. King, R. G. and Stanbury, S. W.: Magnesium metabolism in primary hyperpara- 30. Spencer, R. P.: Intestinal Absorption of Aminoacids. Am. J. Clin. Nutr., 22: 292 thyroidism. Ann. Intern. Med., 62: 1223 (1%5). (1%9). 16. Kramer, H. J., Backer, A., and Kruck, F.: Inhibition of Intestinal Na-K-ATPase 31. Suhadohik, R. I.: Nucleoside Antibiotics p. 43. (Wiley Interscience. New York in experimental uremia. Clin. Chirn. Acta, 50: 13 (1974). 1970). 17. Lifshitz, F., Hawkiis, R. L., Diaz-Bensussen, S., and Wapnir, R. A,: Absorption 32. wapni;, R. A. and Lifshitz, F.: Absorption of amino acids in malnourished rats. of carbohydrates in malnourished rats. J. Nutr., 102: 1303 (1972). J. Nutr., 104: 843 (1974). 18. Longnecker, D. S.: Organ distribution of puromycin in rats. A possible basis for 33. Wilkinson, G. N.: Statistical Estimations in Enzyme Kinetics. Biochem. J., 80: selective cytotoxicity. Lab. Invest., 22: 400 (1970). 324 (1961). 19. Lowry, 0. H., Rosebrough, N. L., Farr, A. L., and Randall, R. J.: Protein 34. Wiseman, G.: Absorption of amino acids in "Handbook of Physiology" Code C. measurements with the Folin phenol reagent. J. Biol. Chem., 193: 265 (1951). F., edit, Section 6, Vol. 3, p. 1277, (Amer Physiol Soc., Washington, D.C., 20. Luft, J. M.: Improvements in Epoxy Resin Embedding Methods. 3 J. Biophys. --1968). --,. Biochem. Cytol., 2: 409 (1961). 35. Yarmolinsky, R. D. and Haba de La, G. L.: Inhibition by puromycin of 21. Malawar, S. J. and Powell, D. W.: An Improved Turbidometric Analysis of amhaacid incorporation into protein. Proc. Nat. Acad. Sci., 45: 172 1 (1 959). Polyethylene Glycol utilizing an Emulsifier. Gastroenterology, 53: 250 (1967). 36. Yssing, M., Jensen, H., and Jarnum, S.: Albumin metabolism and gastrointestinal 22. Nagle, R. B., Bulger, R. E., Stricker, G. E., and Benditt, E. P.: Renal tubular protein loss in children with nephrotic syndrome. Acta Paediatr. Scand., 58: effects of the aminonucleoside of puromycin. Lab. Invest., 26: 558 (1972). 109 (1969). 23. Phang, I. M., Valle, D. L., Fisher, L., and Granger, A,: Puromycin effect on 37. Charles River, Wilmington, Mass. amino acid transport: differential rates of carrier protein turnover. Am. J. 38. Purina Lab Chow, Ralston-Puria Co., St. Louis, Mo. Physiol., 228: 23 (1975). 39. Sigma Chemical Corp., St. Louis. Mo. 24. Sabatini, D. D., Bensch, K., and Barnett, R. J.: Cytochemistry and Electron 40. Harvard Instruments, MiIls, Mo. Microscopy: The preservation of cellular ultrastructure and enzymatic activity 41. New England Nuclear, Coston, Mass. by aldehyde fixation. J. Cell Biol., 171: 19 (1963). 42. J. T. Barker Co., Phillipsburgh, N.J. 25. Salazan de Sousa, J., Guerreiro, 0.. Cunha, A., and Aranjo, J.: The Association 43. Instrumentation Laboratory, Boston, Mass. of Nephrotic Syndrome with Intestinal Lymphangicctasia. Archs. Dis. Child., 44. BUN-TEL, Pfmr, Inc. New York, New York. 43: 245 (1%8). 45. We gratefully acknowledge the assistance of Kristina Mrozinska, Lori Strand and 26. Saunders, S. J. and Isselbacher, K. J.: Intestinal absorption of arninoacids. Rosemary Kemey in the preparation of this manuscript. Gastroenterology, 50: 586 (1966). 46. This investigationwas supported in part by a grant from The Shubert Foundation 27. Schneider, W. C.: Phosphorus compounds in animal tissues. 1. Extraction and and USPHS - Grant 1 SO 8 RR 09128-01A1. estimation of deoxypentose nucleic acid and of pentose nucleic acid. J. Biol. 47. Requests for reprints should be addressed to: Dr. Melinda McVicar, Department Chem., 161: 293 (1945). of Pediatrics, North Shore University Hospital, 300 Community Dr., Manhas- 28. Short, E. M., Elsas, L. J., and Rosenberg. L. E.: Effect of parathyroid hormone set, N.Y. 11030. on renal tubular reabsorption of amino acids. Metabolism, 23: 715 (1974). 48. Received for publication February 11, 1981. 29. Sladen, G. E. and Dawson, A. M.: Interrelationships between the absorption of 49. Accepted for publication December 14, 1982. 0031-3998/83/1709-0737$02.00/0 Vol. 17, No. 9, 1983 PEDIATRIC RESEARCH Printed in U.S.A. Copyright O 1983 International Pediatric Research Foundation, Inc. Enhancement of Sodium Excretion by Substance P during Saline Loading in the Canine Puppy ROBERT D. FILDES,'~' MICHAEL SOLHAUG, NICK TAVANI, JR., GILBERT EISNER, PHILIP CALCAGNO, AND PEDRO A. JOSE Department of Pediatrics, Georgetown University Medical Center, 3800 Reservoir Road, N. W., Washington, D. C. 20007, USA Summary stance P infusion were significantly greater than those observed Saline loading in puppies results in an attenuated natriuresis during saline loading alone. No significant effect on GFR was when compared to the normal response by adult animals to the observed during either saline loading alone or low dose substance same degree of volume expansion. To characterize an eventual P during saline loading. In Protocol 11, the infusion of low dose role for kinins in the diuretic response by puppies to saline loading, substance P during an ongoing saline load enhanced diuresis and two experimental protocols were constructed to evaluate the effect natriuresis to a greater extent than those receiving only a he of substance P infusion during baseline hydration and acute saline load without affecting GFR. The high dose infusion of substance loading. Low dose (10 ngokg-'emin-') infusion of substance P P (100 ng*kg-'-mio-') during baseline hydration resulted in a during basal conditions did not affect urine flow, sodium excretion natriuresis and diuresis that persisted during the addition of saline or glomerular ffltration rate (GFR). The addition of saline loading despite a sigaiflcnat fall in GFR. Saline loading alone resulted in to the ongoing low dose infusion of substance P produced an increased urinary kallikreio activity and the infusion of substance increase in urine flow from 3.73 to 12 @omin-'*g-' kidney weight P (10 ng*kg-'omin-') increased urinary kallikrein activity even and resulted in a marked increase in urinary sodium excretion further. A significant positive correlation between urinary sodium from 110 to 851 CrEq-min-log-' kidney weight. These increases excretion and urine kallikrein activity was found (r = 0.91, P < in urine flow and urinary sodium excretion during low dose sub- 0.01). 738 FILDES ET AL. Abbreviations All animals were infused with a standard electrolyte solution (D~ElgTravenol)at 0.06 ml .min-' .kg-' body weight. A priming GFR, glomenrlar Ntration rate injection of [3H]labeled inulin, 3-5 pCi/kg body weight, was T, tosyl-arginlae followed by a constant infusion of [3H]labeled inulin at a rate of UN.V, absolute urinary excretion sodium 0.06 pCi-min-' . kg-' body weight. Surgical losses were replaced before equilibration and arterial blood gases were monitored The neonate in many species has a characteristic inability to throughout the experiment, with adjustments made in the assisted excrete a saline load as rapidly and efficiently as its adult coun- ventilation to maintain the arterial pH at 7.4, Po2 at 60-90 mmHg terpart (2, 3, 4, 14, 18). Among the factors considered to be and Pcoz at 35 with bicarbonate at 16-22 mEq/liter. Blood important contributors to this phenomenon are a lower basal samples were obtained as midpoint specimen during timed urine GFR, the pattern of intrarenal ditribution of blood flow with a collections and were used for measurement of hematocrit, serum predominance of the juxtamedullary nephrons, and particularly, protein, and plasma sodium as well as inulin concentration. After a greater distal avidity for sodium reabsorption (5, 18, 19,31). The a 1-h equilibration period, three timed urine collections of ap- latter has been demonstrated in both human neonates and puppies proximately 5 min each were obtained before any fluid or drug and it has been suggested that there is a heterogenous development manipulations (baseline Period I) for inulin clearances and frac- of the nephron with a relative structural and hnctional predomi- tional excretion of sodium. Subsequently, the manipulations of nance of the distal tubule in early life, which would respond to the animals depended upon the experimental protocol followed. the high aldosterone levels characteristic of the neonate (5, 15,31, Protocol I (Baseline-test inftrsion-saline load). The purpose of 32, 34, 37). this protocol was to measure the renal response to an infusion of There are several hormones locally formed and released that substance P or placebo (vehicle-D6Ea) before (Period 11) and have been thought to modify sodium excretion by the kidney. In subsequently during saline loading (Period 111). In three separate particular, the role of the renal kallikrein system in the regulation groups of puppies, after the baseline clearance period, the animal of sodium and water excretion by the kidney has evoked great received either D5& alone (control group, n = 7), Dab8 with interest (8, 20, 23, 25). Kallidin and/or bradykinin may facilitate substance P at 10 ng. kg-' emin-' (experimental rou A, n = 7) sodium excretion during periods of natriuresis (23, 35). Urinary or Dab with substance P at 100 ng. kg-' min4 (E;perimental kallikrein levels are low in infants, and it is therefore plausible group B, n = 7). The overall rate of delivery of baseline fluids was that decreased activity of the kallikrein/kinin system in the new- maintained at 0.06 ml. kg-'.min-' throughout the remainder of born may contribute to the neonate's lesser ability to excrete a salt the experiment. The test solutions were coded so that the experi- load (36). The purpose of our study was to evaluate the effect of menter was unaware of their identities. Urinary losses were not substance P, an undecapeptide known to increase the release or replaced.
Load more

Recommended publications
  • Properties of Chemically Oxidized Kininogens*
    Vol. 50 No. 3/2003 753–763 QUARTERLY Properties of chemically oxidized kininogens*. Magdalena Nizio³ek, Marcin Kot, Krzysztof Pyka, Pawe³ Mak and Andrzej Kozik½ Faculty of Biotechnology, Jagiellonian University, Kraków, Poland Received: 30 May, 2003; revised: 01 August, 2003; accepted: 11 August, 2003 Key words: bradykinin, N-chlorosuccinimide, chloramine-T, kallidin, kallikrein, reactive oxygen species Kininogens are multifunctional proteins involved in a variety of regulatory pro- cesses including the kinin-formation cascade, blood coagulation, fibrynolysis, inhibi- tion of cysteine proteinases etc. A working hypothesis of this work was that the prop- erties of kininogens may be altered by oxidation of their methionine residues by reac- tive oxygen species that are released at the inflammatory foci during phagocytosis of pathogen particles by recruited neutrophil cells. Two methionine-specific oxidizing reagents, N-chlorosuccinimide (NCS) and chloramine-T (CT), were used to oxidize the high molecular mass (HK) and low molecular mass (LK) forms of human kininogen. A nearly complete conversion of methionine residues to methionine sulfoxide residues in the modified proteins was determined by amino acid analysis. Production of kinins from oxidized kininogens by plasma and tissue kallikreins was significantly lower (by at least 70%) than that from native kininogens. This quenching effect on kinin release could primarily be assigned to the modification of the critical Met-361 residue adja- cent to the internal kinin sequence in kininogen. However, virtually no kinin could be formed by human plasma kallikrein from NCS-modified HK. This observation sug- gests involvement of other structural effects detrimental for kinin production. In- deed, NCS-oxidized HK was unable to bind (pre)kallikrein, probably due to the modifi- cation of methionine and/or tryptophan residues at the region on the kininogen mole- cule responsible for the (pro)enzyme binding.
    [Show full text]
  • Sized Neuropeptides
    M ETHODS IN MOLECULAR BIOLOGY™ Series Editor John M. Walker School of Life Sciences University of Hertfordshire Hatfield, Hertfordshire, AL10 9AB, UK For further volumes: http://www.springer.com/series/7651 Neuropeptides Methods and Protocols Edited by Adalberto Merighi Dipartimento di Morfofisiologia Veterinaria, Università degli Studi di Torino, Grugliasco, TO, Italy; Istituto Nazionale di Neuroscienze (INN), Università degli Studi di Torino, Grugliasco, TO, Italy Editor Adalberto Merighi Dipartimento di Morfofisiologia Veterinaria Università degli Studi di Torino and Istituto Nazionale di Neuroscienze (INN) Università degli Studi di Torino Grugliasco, TO, Italy [email protected] Please note that additional material for this book can be downloaded from http://extras.springer.com ISSN 1064-3745 e-ISSN 1940-6029 ISBN 978-1-61779-309-7 e-ISBN 978-1-61779-310-3 DOI 10.1007/978-1-61779-310-3 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011936011 © Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,039,660 Leonard Et Al
    United States Patent (19) 11 Patent Number: 5,039,660 Leonard et al. (45. Date of Patent: Aug. 13, 1991 54 PARTIALLY FUSED PEPTIDE PELLET 4,667,014 5/1987 Nestor, Jr. et al. ................. 514/800 4,801,577 / 1989 Nestor, Jr. et al. ................. 54/800 75 Inventors: Robert J. Leonard, Lynnfield, Mass.; S. Mitchell Harman, Ellicott City, Primary Examiner-Lester L. Lee Md. Attorney, Agent, or Firm-Wolf, Greenfield & Sacks 73 Assignee: Endocon, Inc., South Walpole, Mass. (57) ABSTRACT 21 Appl. No.: 163,328 A bioerodible pellet capable of administering an even 22 Filed: Mar. 2, 1988 and continuous dose of a peptide over a period of up to a year, when subcutaneously implanted, is provided. (51) Int. Cl’.............................................. C07K 17/08 (52 U.S.C. .......................................... 514/8; 514/12; The bioerodible implant is a partially-fused pellet, 514/14: 514/15; 514/16; 514/17; 514/18; which pellet has a peptide drug homogeneously-bound 514/19; 514/800 in a matrix of a melted and recrystallized, nonpolymer Field of Search ................... 514/8, 12, 14, 15, 16, carrier. Preferably, the nonpolymer carrier is a steroid (58) and in particular is cholesterol or a cholesterol deriva 514/17, 18, 19, 800 tive. In one embodiment, the peptide drug is growth (56) References Cited hormone-releasing hormone. A method for making the U.S. PATENT DOCUMENTS bioerodible pellet also is provided. 4,164,560 8/1979 Folkman et al. .................... 424/427 '4,591,496 5/1986 Cohen et al. .......................... 424/78 13 Claims, 4 Drawing Sheets U.S. Patent Aug.
    [Show full text]
  • Akhtar Saeed Medical and Dental College, Lhr
    STUDY GUIDE PHARMACOLOGY 3RD YEAR MBBS 2021 AKHTAR SAEED MEDICAL AND DENTAL COLLEGE, LHR 1 Table of contents s.No Topic Page No 1. Brief introduction about study guide 03 2. Study guide about amdc pharmacology 04 3. Learning objectives at the end of each topic 05-21 4. Pharmacology classifications 22-59 5. General pharmacology definitions 60-68 6. Brief introduction about FB PAGE AND GROUP 69-70 7. ACADEMIC CALENDER (session wise) 72 2 Department of pharmacology STUDY GUIDE? It is an aid to: • Inform students how student learnIng program of academIc sessIon has been organized • help students organIze and manage theIr studIes throughout the session • guIde students on assessment methods, rules and regulatIons THE STUDY GUIDE: • communIcates InformatIon on organIzatIon and management of the course • defInes the objectIves whIch are expected to be achIeved at the end of each topic. • IdentIfIes the learning strategies such as lectures, small group teachings, clinical skills, demonstration, tutorial and case based learning that will be implemented to achieve the objectives. • provIdes a lIst of learnIng resources such as books, computer assIsted learning programs, web- links, for students to consult in order to maximize their learning. 3 1. Learning objectives (at the end of each topic) 2. Sources of knowledge: i. Recommended Books 1. Basic and Clinical Pharmacology by Katzung, 13th Ed., Mc Graw-Hill 2. Pharmacology by Champe and Harvey, 2nd Ed., Lippincott Williams & Wilkins ii. CDs of Experimental Pharmacology iii. CDs of PHARMACY PRACTICALS iv. Departmental Library containing reference books & Medical Journals v. GENERAL PHARMACOLOGY DFINITIONS vi. CLASSIFICATIONS OF PHARMACOLOGY vii.
    [Show full text]
  • (A-LAP)/ER-Aminopeptidase-1
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 580 (2006) 1833–1838 Reduced activity of the hypertension-associated Lys528Arg mutant of human adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase-1 Yoshikuni Gotoa,b, Akira Hattoria, Yasuhiro Ishiib, Masafumi Tsujimotoa,* a Laboratory of Cellular Biochemistry, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan b Laboratory of Applied Protein Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-0054, Japan Received 15 December 2005; revised 21 January 2006; accepted 15 February 2006 Available online 24 February 2006 Edited by Irmgard Sinning searching databases [3,4]. Structural and phylogenetic analyses Abstract The adipocyte-derived leucine aminopeptidase (A- LAP)/ER aminopeptidase-1 is a multi-functional enzyme belong- indicated that P-LAP, A-LAP and L-RAP are most closely re- ing to the M1 family of aminopeptidases. It was reported that the lated among the M1 family of aminopeptidases, which contain polymorphism Lys528Arg in the human A-LAP gene is associ- GAMEN and HEXXH(X)18E consensus motifs. Therefore we ated with essential hypertension. In this study, the role of proposed that they should be classified into ‘‘the oxytocinase Lys528 in the enzymatic activity of human A-LAP was exam- subfamily of M1 aminopeptidases’’ [5]. ined by site-directed mutagenesis. Among non-synonymous poly- A-LAP is a multi-functional aminopeptidase shown to play morphisms tested, only Lys528Arg reduced enzymatic activity. roles in the regulation of blood pressure, angiogenesis and The replacement of Lys528 with various amino acids including antigen presentation to MHC class I molecules [5–9].
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2015/0050270 A1 Li Et Al
    US 2015.005O270A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0050270 A1 Li et al. (43) Pub. Date: Feb. 19, 2015 (54) ANTIBODIES TO BRADYKININ B1 Publication Classification RECEPTOR LIGANDS (51) Int. Cl. (71) Applicant: Sanofi, Paris (FR) C07K 6/28 (2006.01) A647/48 (2006.01) (72) Inventors: Han Li, Yardley, PA (US); Dorothea Kominos, Millington, NJ (US); Jie (52) U.S. Cl. Zhang, Cambridge, MA (US); Alla CPC ........... C07K 16/28 (2013.01); A61K 47/48007 Pritzker, Cambridge, MA (US); (2013.01); C07K 2317/92 (2013.01); C07K Matthew Davison, Cambridge, MA 2317/565 (2013.01); C07K 2317/76 (2013.01); (US); Nicolas Baurin, Arpajon (FR); C07K 231 7/24 (2013.01); A61K 2039/505 Govindan Subramanian, Belle Mead, (2013.01) NJ (US); Xin Chen, Edison, NJ (US) USPC .................. 424/133.1; 530/387.3; 530/3917; 536/23.53; 435/320.1; 435/334: 435/69.6 (73) Assignee: SANOFI, Paris (FR) (21) Appl. No.: 14/382,798 (57) ABSTRACT (22) PCT Filed: Mar. 15, 2013 The invention provides antibodies that specifically bind to (86). PCT No.: PCT/US13A31836 Kallidin ordes-Arg10-Kallidin. The invention also provides S371 (c)(1), pharmaceutical compositions, as well as nucleic acids encod (2) Date: Sep. 4, 2014 ing anti-Kallidin ordes-Arg10-Kallidin antibodies, recombi nant expression vectors and host cells for making such anti Related U.S. Application Data bodies, or fragments thereof. Methods of using antibodies of (60) Provisional application No. 61/616,845, filed on Mar. the invention to modulate Kallidin or des-Arg10-Kallidin 28, 2012.
    [Show full text]
  • Capturing Peptide–GPCR Interactions and Their Dynamics
    molecules Review Capturing Peptide–GPCR Interactions and Their Dynamics Anette Kaiser * and Irene Coin Faculty of Life Sciences, Institute of Biochemistry, Leipzig University, Brüderstr. 34, D-04103 Leipzig, Germany; [email protected] * Correspondence: [email protected] Academic Editor: Paolo Ruzza Received: 31 August 2020; Accepted: 9 October 2020; Published: 15 October 2020 Abstract: Many biological functions of peptides are mediated through G protein-coupled receptors (GPCRs). Upon ligand binding, GPCRs undergo conformational changes that facilitate the binding and activation of multiple effectors. GPCRs regulate nearly all physiological processes and are a favorite pharmacological target. In particular, drugs are sought after that elicit the recruitment of selected effectors only (biased ligands). Understanding how ligands bind to GPCRs and which conformational changes they induce is a fundamental step toward the development of more efficient and specific drugs. Moreover, it is emerging that the dynamic of the ligand–receptor interaction contributes to the specificity of both ligand recognition and effector recruitment, an aspect that is missing in structural snapshots from crystallography. We describe here biochemical and biophysical techniques to address ligand–receptor interactions in their structural and dynamic aspects, which include mutagenesis, crosslinking, spectroscopic techniques, and mass-spectrometry profiling. With a main focus on peptide receptors, we present methods to unveil the ligand–receptor contact interface and methods that address conformational changes both in the ligand and the GPCR. The presented studies highlight a wide structural heterogeneity among peptide receptors, reveal distinct structural changes occurring during ligand binding and a surprisingly high dynamics of the ligand–GPCR complexes. Keywords: GPCR activation; peptide–GPCR interactions; structural dynamics of GPCRs; peptide ligands; crosslinking; NMR; EPR 1.
    [Show full text]
  • Comprehensive GPCR Assay Solutions for Drug Discovery
    GPCR Screening with Confidence Comprehensive GPCR Assay Solutions for Drug Discovery Why go anywhere else? Why go anywhere else? We cover the entire range of GPCR assay possibilities. Shop at the GPCR Super Store. From PerkinElmer — your one stop solution provider. PerkinElmer — a Source of Confidence for Your GPCR Research and Discovery G-Protein Coupled Receptors (GPCRs) continue to be significant therapeutic Contents targets, and thus GPCR assays and screening campaigns remain major •Assay Platforms for GPCR Binding Assays ...........2 components of drug discovery research • NEN Radioligands for GPCR Binding Assays .......4 programs worldwide. The need for • Cloned Receptors for GPCR Binding Assays.........4 reliable, proven, and versatile assay • Adenylyl Cyclase Activation/Inhibition and technologies and reagents is a key cAMP Quantitation ................................................5 component for successful and productive •Detection Instrumentation to Measure research. That’s why PerkinElmer GPCR Assays ........................................................11 has assembled the world’s most •Ordering Information: comprehensive product offering for DELFIA Ligands and Reagents.............................16 GPCR research and drug discovery, covering the entire range of GPCR GPCR-Specific NEN Radioligands.......................17 assay possibilities. SignalScreen® Cloned Receptors .........................18 Membrane Target Systems Cloned Receptors .....23 Our products and expertise span receptor ligand FlashBlue™ Scintillating
    [Show full text]
  • Natural and Synthetic Inhibitors of Kallikrein-Related Peptidases (Klks)
    Biochimie 92 (2010) 1546e1567 Contents lists available at ScienceDirect Biochimie journal homepage: www.elsevier.com/locate/biochi Review Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs) Peter Goettig a,*, Viktor Magdolen b, Hans Brandstetter a a Division of Structural Biology, Department of Molecular Biology, University of Salzburg, Billrothstrasse 11, 5020 Salzburg, Austria b Klinische Forschergruppe der Frauenklinik, Klinikum rechts der Isar der TU München, Ismaninger Strasse 22, 81675 München, Germany article info abstract Article history: Including the true tissue kallikrein KLK1, kallikrein-related peptidases (KLKs) represent a family of fifteen Received 24 February 2010 mammalian serine proteases. While the physiological roles of several KLKs have been at least partially Accepted 29 June 2010 elucidated, their activation and regulation remain largely unclear. This obscurity may be related to the fact Available online 6 July 2010 that a given KLK fulfills many different tasks in diverse fetal and adult tissues, and consequently, the timescale of some of their physiological actions varies significantly. To date, a variety of endogenous þ Keywords: inhibitors that target distinct KLKs have been identified. Among them are the attenuating Zn2 ions, Tissue kallikrein fi active site-directed proteinaceous inhibitors, such as serpins and the Kazal-type inhibitors, or the huge, Speci city pockets fi Inhibitory compound unspeci c compartment forming a2-macroglobulin. Failure of these inhibitory systems can lead to certain Zinc pathophysiological conditions. One of the most prominent examples is the Netherton syndrome, which is Rule of five caused by dysfunctional domains of the Kazal-type inhibitor LEKTI-1 which fail to appropriately regulate KLKs in the skin.
    [Show full text]
  • Contributions to the Evolution of Blood Pressure Regulation
    Z. klin. Chem. u. klin. Biochem. 7. Jg., S. 464—466, September 1969 Contributions to the Evolution of Blood Pressure Regulation Part II: Evidence for the Absence of Kinin-like Polypeptides Released by Proteolytic Enzymes for Blood Pressure Regulation in Fish By ROSMARIE VOGEL, H. SCHIEVELBEIN, W. LORENZ and E. WERLE, with the assistance of A. SCHMAL From the Institut fur Klinische Chemie mid Klinische Biochemie der Universitat Miinchen (Direktor: Prof. Dr. Dr. E. Werle) (Fingcgangen am 9. Mai 1969) The intravenous injection of Padutin, bradykinin, kallidin and eledoisin is without effect on the blood pressure of cartilagenous and teleost fish. Preparations of fish pancreas and fish serum prepared in the same manner as organs of mammals and birds for prekallikrein/ kallikrcin or kininogen/kinin were also without effect. Therefore in fish the existence of a kallikrein-kinin like circulation regulating system can be excluded. Die intravenose Injektion von Psfdutin, Bradykinin, Kallidin und Eledoisin hat keine Wirkung auf den Blutdruck bei Knorpel- und Knochenfischen (Katzenhai und Wels). Auch Praparate aus Fischpankrcas und Fischserum, die gleichermaftcn wie Saugctier- und Vogclor- ganc aufgearbcitct waren und demnach PraekalHkrein bzw. Kallikrcin oder Kininogen bzw. Kinin enthalten muftten, waren ebenfalls wTir kungslos. Die Existenz eines blutdruckwirksamen, Kallikrein-Kinin-ahnlichcn Systems kann demnach bei Fischcn ausgeschlossen werden. In the first part of this paper we described the presence fresh water. Acetone — dried powder was prepared by mixing one of an adrenergic system in cartilagenous and teleost part of pancreas homogenate with one part of acetone; drying was performed at room temperature. fish (1). Preparation of a kinin-like component from fish: serum from In mammals and birds in addition to the adrenergic fish was incubated with fish pancreas homogenate or trypsin system for blood pressure regulation, there exist two according to known methods (5).
    [Show full text]
  • Properties of Chemically Oxidized Kininogens*
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Jagiellonian Univeristy Repository Vol. 50 No. 3/2003 753–763 QUARTERLY Properties of chemically oxidized kininogens*. Magdalena Nizio³ek, Marcin Kot, Krzysztof Pyka, Pawe³ Mak and Andrzej Kozik½ Faculty of Biotechnology, Jagiellonian University, Kraków, Poland Received: 30 May, 2003; revised: 01 August, 2003; accepted: 11 August, 2003 Key words: bradykinin, N-chlorosuccinimide, chloramine-T, kallidin, kallikrein, reactive oxygen species Kininogens are multifunctional proteins involved in a variety of regulatory pro- cesses including the kinin-formation cascade, blood coagulation, fibrynolysis, inhibi- tion of cysteine proteinases etc. A working hypothesis of this work was that the prop- erties of kininogens may be altered by oxidation of their methionine residues by reac- tive oxygen species that are released at the inflammatory foci during phagocytosis of pathogen particles by recruited neutrophil cells. Two methionine-specific oxidizing reagents, N-chlorosuccinimide (NCS) and chloramine-T (CT), were used to oxidize the high molecular mass (HK) and low molecular mass (LK) forms of human kininogen. A nearly complete conversion of methionine residues to methionine sulfoxide residues in the modified proteins was determined by amino acid analysis. Production of kinins from oxidized kininogens by plasma and tissue kallikreins was significantly lower (by at least 70%) than that from native kininogens. This quenching effect on kinin release could primarily be assigned to the modification of the critical Met-361 residue adja- cent to the internal kinin sequence in kininogen. However, virtually no kinin could be formed by human plasma kallikrein from NCS-modified HK. This observation sug- gests involvement of other structural effects detrimental for kinin production.
    [Show full text]
  • Supplementary Table 1: Screening Library Compound List
    Supplementary Table 1: Screening library compound list # ligand 1 Ac2-26 (N-terminal fragment of annexin-1, lipocortin-1) 2 Ac2-12 (N-terminal fragment of annexin-1, lipocortin-1) 3 Boc-Phe-Leu-Phe-Leu-Phe 4 LL37 (Human) 5 N-Formyl-Nle-Leu-Phe-Nle-Tyr-Lys 6 N-Formyl-Met-Ile-Leu-Phe 7 N-Formyl-Met-Ile-Phe-Leu 8 N-Formyl-Met-Leu-Ile-Phe 9 N-Formyl-Met-Leu-Phe 10 N-Formyl-Met-Leu-Phe-Ile 11 N-Formyl-Met-Leu-Phe-Lys 12 N-Formyl-Met-Gln-Leu-Gly-Arg 13 WKYMVM 14 WKYMVm 15 Apelin-36 (Human) 16 Apelin-36 (Bovine) 17 Apelin-36 (Rat) 18 Apelin-19 (Human, Bovine) 19 Apelin-17 (Human, Bovine) 20 Apelin-16 (Human, Bovine) 21 Apelin-15 (Human, Bovine) 22 Apelin-13 (Human, Bovine) 23 Apelin-13, [pGlu1] (Human, Bovine) 24 Apelin (23-57) -Prepro (Human) 25 Apelin-12 (Human, Bovine) 26 Allatostatin 1 27 Allatostatin 3 28 Allatostatin 4 29 Adipokinetic Hormone (AKH) (Locust) 30 Adipokinetic Hormone (Heliothis zea and Manduca sexta) 31 Adipokinetic Hormone (Taa-AKH) (Tabanus atratus) 32 Adipokinetic Hormone II (Schistocera gregaria) 33 Adipokinetic Hormone G (AKH-G) (Gryllus bimaculatus) 34 Litorin-Rohdei (AF 1 Ascaris suum) 35 Angiotensin I (Human) 36 Angiotensin I (1-9) (Human) 37 Angiotensin I, [Des-Asp1-] (Human) 38 Angiotensin II (Human) 39 Angiotensin II [Sar1] 40 D-Pro7-Angiotensin-(1-7) 41 Angiotensin II, [Sar1,Ala8] 42 Angiotensin II [Sar1 Ile8] 43 Angiotensin II (1-7) 44 Angiotensin II [Sar1Val5Ala8] (Human Canine Rat Mouse) 45 Angiotensin IV [AT-II (3-8)] 46 Angiotensin II (4-8) (Human) 47 Angiotensin II, [Des-Asp1-] (Angiotensin III) (Human) 48
    [Show full text]