Intestinal Medium PBS 0,01M Ph 7'4

Total Page:16

File Type:pdf, Size:1020Kb

Intestinal Medium PBS 0,01M Ph 7'4 US 20080317666A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0317666 A1 Fattal et al. (43) Pub. Date: Dec. 25, 2008 (54) COLONIC DELIVERY OF ACTIVE AGENTS Publication Classi?cation (51) Int. Cl. (76) Inventors: Elias Fattal, Paris (FR); Antoine A611; 9/00 (2006.01) Andremont, Malakoff (FR); A611; 49/00 (2006.01) Patrick Couvreur, A611; 51/12 (2006.01) Villebon-sur-Yvette (FR); Sandrine A61P 1/00 (2006.01) Bourgeois, Lyon (FR) (52) us. c1. ........................ .. 424/111; 424/423; 424/9.1 (57) ABSTRACT Correspondence Address: Drug delivery devices that are orally administered, and that David S. Bradin release active ingredients in the colon, are disclosed. In one Womble Carlyle Sandridge & Rice embodiment, the active ingredients are those that inactivate P.O.Box 7037 antibiotics, such as macrolides, quinolones and beta-lactam Atlanta, GA 30359-0037 (US) containing antibiotics. One example of a suitable active agent is an enzyme such as beta-lactamases. In another embodi ment, the active agents are those that speci?cally treat colonic (21) Appl. No.: 11/628,832 disorders, such as Chrohn’s Disease, irritable boWel syn drome, ulcerative colitis, colorectal cancer or constipation. (22) PCT Filed: Feb. 9, 2006 The drug delivery devices are in the form of beads of pectin, crosslinked With calcium and reticulated With polyethylene imine. The high crosslink density of the polyethyleneimine is (86) PCT No.: PCT/GB06/00448 believed to stabilize the pectin beads for a su?icient amount of time such that a substantial amount of the active ingredi § 371 (0X1)’ ents can be administered directly to the colon. Advanta (2), (4) Date: Mar. 3, 2008 geously, the amount of polyethyleneimine is su?icient to alloW a substantial portion of the pectin beads to pass through Related US. Application Data the gastrointestinal tract to the colon Without releasing the active agent, and is also suf?cient such that the pectin beads (60) Provisional application No. 60/651,342, ?led on Feb. are suf?ciently degraded in the colon to release an effective 9, 2005. amount of the active agent. 12 . “OH ‘I [PEI] 0% 1O ' ‘ IO.60% 8 . u _ 0.70% .E' 6 P I 0.50% 4 ~ . _ é - m 0.90% .‘ it; o 0 - ‘ ' . ' I 1 /o ‘ Gastric Medium Intestinal medium PBS 0,01M pH 7'4 ‘ Media Patent Application Publication Dec. 25, 2008 Sheet 1 0f 8 US 2008/0317666 A1 £36I O\eomdE Q?n;:2.$0 I.EXA. or$00.0I @. $2.0 8.285_.wmm .252552.82535:n23.03. 282, r@SmE T.“?x;..I<,._...,.w .o i.. .W. ..- . @ N- mil Patent Application Publication Dec. 25, 2008 Sheet 2 0f 8 US 2008/0317666 Al NmSmE 2.3m2°55 3D223m Patent Application Publication Dec. 25, 2008 Sheet 3 0f 8 US 2008/0317666 A1 8.8. I2I 8.02:2- mSmE.m 2550m-86.,. .. mm52a$3.mm.56553 89?228m.B w 8.812m. .862m 5.5 W-88 m %. Patent Application Publication Dec. 25, 2008 Sheet 4 0f 8 US 2008/0317666 A1 510018 10 3w out/1n Patent Application Publication Dec. 25, 2008 Sheet 5 0f 8 US 2008/0317666 A1 .. ......h_.h..qm . 4: wk. mSmE.m 22;?223m. =62.3m Patent Application Publication Dec. 25, 2008 Sheet 6 0f 8 US 2008/0317666 A1 3,3522$? 939m@ Patent Application Publication Dec. 25, 2008 Sheet 7 0f 8 US 2008/0317666 A1 Figure7 WholeBeads, BeadsCut Patent Application Publication Dec. 25, 2008 Sheet 8 0f 8 US 2008/0317666 A1 2am<75uwoiomiv<750532.2495 wSmEw 32823.3nas?ammgm5358mEQE5B3233253a$5.3<ZQ 2.3a.33.:355322:53.. .8S 2:F Tom VNq pa?mwoipm J0 i?ogelnsdeaug. % US 2008/0317666 A1 Dec. 25, 2008 COLONIC DELIVERY OF ACTIVE AGENTS though this diarrhoea is generally not serious and quickly ceases, either spontaneously, or on completion of treatment, it FIELD OF THE INVENTION is all the same badly received by patients and adds to the discomfort of the base illness for Which the antibiotic Was [0001] The present invention is in the area of oral drug prescribed; delivery devices that administer active agents to the colon. [0007] 2. perturbation of the functions of resistance to colo niZation by exogenic bacteria (or “barrier effect”) With pos BACKGROUND OF THE INVENTION sibilities of risk from infection, for example, alimentary sal [0002] Drug delivery devices that speci?cally deliver active monella intoxication (Holmberg S. D. et al. (1984) Drug agents to the colon have been recognized as having important resistant Salmonella from animals fed antimicrobials, New therapeutic advantages. A large number of colonic conditions England Journal ofMedicine, 311, 617); could effectively be treated more ef?caciously if the active [0008] 3. selection of microorganisms resistant to the anti ingredient is released locally. Examples of such colonic dis biotic. The latter can be ofvarious types: orders include Crohn’s disease, ulcerative colitis, colorectal [0009] a) ?rst they can be pathogenic bacteria such as for cancer and constipation. example, Clostridium di?icile, a species capable of secreting [0003] Colonic release can also bene?t patients When, from toxins causing a form of colitis knoWn as pseudomembranous a therapeutic point of vieW, a delay in absorption is necessary. (Bartlett J. G. (1997) Clostridium di?icile infection: patho Examples include the treatment of disorders such as noctur physiology and diagnosis, Seminar in Gastrointestinal Dis nal asthma or angor (Kinget R. et al. (1998), Colonic Drug ease, 8, 12); Targeting, Journal ofDrug Targeting, 6, 129). [0010] b) they can also be microorganisms that are rela [0004] Colonic release can also be used to administer thera tively Weakly pathogenic, but Whose multiplication can lead peutically active polypeptides. Polypeptides are typically to an associated infection (vaginal Candidosis or Escherichia administered by injection, because they are degraded in the coli resistant cystitis). stomach. Because injection is painful, research efforts have [0011] c) they can ?nally be non-pathogenic commensal focused on using the colon as a site of absorption for active drug resistant bacteria Whose multiplication and fecal elimi polypeptides, including analgesics, contraceptives, vaccines, nation is going to increase dissemination in the environment. insulin, and the like. The absorption of polypeptides in the NoW, these resistant commensal bacteria can constitute an colon appears effectively better than in other sites in the important source of mechanisms of drug resistance for patho digestive tract. This is particularly due to the relatively Weak genic species. This risk is currently considered seminal in proteolytic activity in the small intestine and the absence of terms of the disquieting character of the evolution toWards peptidasic activity associated With the membrane of the drug multiresistance by numerous species pathogenic for colonic epithelial cells. humans. [0005] During administration of antibiotics by mouth, they [0012] Numerous strategies exploiting the diverse physi pass through the stomach and are then absorbed in the small ological parameters of the digestive tract have thus been intestine to diffuse in the Whole organism and treat the infec envisioned With the aim of releasing active ingredients in the tious outbreak site for Which they have been administered. All colon. These strategies have focused on drug delivery systems the same, a fraction of antibiotics ingested (Whereof the based on (1) using polymers that are sensitive to variations in importance varies With the characteristics of each type of pH, (2) time-dependent drug release forms, (3) prodrugs or antibiotics) is not absorbed and continues its progress to the polymers degradable by bacteria in the intestinal ?ora. colon before being eliminated in the stool. These residual [0013] It Would be advantageous to have additional drug antibiotics are reunited, in the large intestine, by a fraction of delivery devices Which can administer active agents to the the antibiotics absorbed, but Which are re-excreted in the colon. It Would also be desirable to have drug delivery devices digestive tract by means of biliary elimination. This fraction for reducing the quantity of residual antibiotics arriving at the is of variable importance as a function of metabolism and colon after oral or parenteral antibiotic therapy. The present Ways of elimination of each antibiotic. Finally, for certain invention provides such drug delivery devices. antibiotics, a fraction of the dose absorbed is eliminated directly via intestinal mucous in the lumen of the digestive SUMMARY OF THE INVENTION tract. Thus, since the antibiotics had been administered orally or parenterally, a residual active fraction is generally found in [0014] Oral drug delivery devices that release active agents the colon. This is true, to varying degrees, for the greater in the colon, are disclosed. In one embodiment, the active majority of families of antibiotics utiliZed in therapeutics, the agents are those that inactivate antibiotics, such as mac sole notable exception being the family of amino-glycosides rolides, quinolones and beta-lactam containing antibiotics. for Which intestinal excretion is negligible. For other antibi One example of a suitable active agent is an enZyme such as otics, intestinal excretion of a residual antibiotic activity is beta-lactamases. In another embodiment, the active agents going to have different consequences, all harmful. In effect, in are those that speci?cally treat colonic disorders, such as the colon there is a complex and very dense bacterial ecosys ulcerative colitis, colorectal cancer, Chrohn’s Disease, irri tem (several hundreds of different bacterial species; more table boWel syndrome, and constipation. The active ingredi than 101 1 bacteria per gram of colonic content) Which is going ents can be hydrosoluble or liposoluble. Depending on the to be affected by the arrival of active antibiotic residues. The active agent, the drug delivery devices can be used in thera folloWing can be observed: peutics or in diagnostics.
Recommended publications
  • Amylase Release from Rat Parotid Gland Slices C.L
    Br. J. P!harmnic. (1981) 73, 517-523 THE EFFECTS OF SUBSTANCE P AND RELATED PEPTIDES ON a- AMYLASE RELEASE FROM RAT PAROTID GLAND SLICES C.L. BROWN & M.R. HANLEY MRC Neurochemical Pharmacology Unit, Medical Research Council Centre, Medical School, Hills Road, Cambridge CB2 2QH 1 The effects of substance P and related peptides on amylase release from rat parotid gland slices have been investigated. 2 Supramaximal concentrations (1 F.M) of substance P caused enhancement of amylase release over the basal level within 1 min; this lasted for at least 40 min at 30°C. 3 Substance P-stimulated amylase release was partially dependent on extracellular calcium and could be inhibited by 50% upon removal of extracellular calcium. 4 Substance P stimulated amylase release in a dose-dependent manner with an ED50 of 18 nm. 5 All C-terminal fragments of substance P were less potent than substance P in stimulating amylase release. The C-terminal hexapeptide of substance P was the minimum structure for potent activity in this system, having 1/3 to 1/8 the potency of substance P. There was a dramatic drop in potency for the C-terminal pentapeptide of substance P or substance P free acid. Physalaemin was more potent than substance P (ED50 = 7 nM), eledoisin was about equipotent with substance P (ED5o = 17 nM), and kassinin less potent than substance P (ED50 = 150 nM). 6 The structure-activity profile observed is very similar to that for stimulation of salivation in vivo, indicating that the same receptors are involved in mediating these responses.
    [Show full text]
  • V·M·I University Microfilms International a Bell & Howell Information Company 300 North Zeeb Road, Ann Arbor
    Characterization of the cloned neurokinin A receptor transfected in murine fibroblasts Item Type text; Dissertation-Reproduction (electronic) Authors Henderson, Alden Keith. Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 27/09/2021 18:29:56 Link to Item http://hdl.handle.net/10150/185828 1/. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note. will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy.
    [Show full text]
  • Genscript Product Catalog 2013-2014 Genscript Product Catalog
    GenScript Product Catalog 2013-2014 GenScript Product Catalog www.genscript.com GenScript USA Inc. 860 Centennial Ave. Piscataway, NJ 08854USA Tel: 1-732-885-9188 / 1-732-885-9688 Toll-Free Tel: 1-877-436-7274 Fax: 1-732-210-0262 / 1-732-885-5878 Email: [email protected] Nucleic Acid Purification and Analysis Business Development Tel: 1-732-317-5088 PCR PCR and Cloning Email: [email protected] Protein Analysis Antibodies 2013-2014 Peptides Welcome to GenScript GenScript USA Incorporation, founded in 2002, is a fast-growing biotechnology company and contract research organization (CRO) specialized in custom services and consumable products for academic and pharmaceutical research. Built on our assembly-line mode, one-stop solutions, continuous improvement, and stringent IP protection, GenScript provides a comprehensive portfolio of products and services at the most competitive prices in the industry to meet your research needs every day. Over the years, GenScript’s scientists have developed many innovative technologies that allow us to maintain our position at the cutting edge of biological and medical research while offering cost-effective solutions for customers to accelerate their research. Our advanced expertise includes proprietary technology for custom gene synthesis, OptimumGeneTM codon optimization technology, CloneEZ® seamless cloning technology, FlexPeptideTM technology for custom peptide synthesis, BacPowerTM technology for protein expression and purification, T-MaxTM adjuvant and advanced nanotechnology for custom antibody production, as well as our ONE-HOUR WesternTM detection system and eStain® protein staining system. GenScript offers a broad range of reagents, optimized kits, and system solutions to help you unravel the mysteries of biology. We also provide a comprehensive portfolio of customized services that include Bio-Reagent, Bio-Assay, Lead Optimization, and Antibody Drug Development which can be effectively integrated into your value chain and your operations.
    [Show full text]
  • Entropy-Driven Binding of Opioid Peptides Induces a Large Domain Motion in Human Dipeptidyl Peptidase III
    Entropy-driven binding of opioid peptides induces a large domain motion in human dipeptidyl peptidase III Gustavo A. Bezerraa, Elena Dobrovetskyb, Roland Viertlmayra, Aiping Dongb, Alexandra Binterc, Marija Abramic´d, Peter Macherouxc, Sirano Dhe-Paganonb,e, and Karl Grubera,1 aInstitute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria; eDepartment of Physiology and bStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada M5G 1L7; cInstitute of Biochemistry, Graz University of Technology, A-8010 Graz, Austria; and dDivision of Organic Chemistry and Biochemistry, Ruđer Boskovic Institute, 10002 Zagreb, Croatia Edited by William W. Bachovchin, Tufts University School of Medicine, Boston, MA, and accepted by the Editorial Board March 9, 2012 (received for review November 2, 2011) Opioid peptides are involved in various essential physiological of action compared with morphine, spinorphin is an analgesic, processes, most notably nociception. Dipeptidyl peptidase III (DPP potentially useful for pain treatment in morphine-resistant cases III) is one of the most important enkephalin-degrading enzymes (14). This opioid peptide was also shown to be a potent and se- associated with the mammalian pain modulatory system. Here we lective antagonist of the receptor P2X3, which is involved in pain describe the X-ray structures of human DPP III and its complex with signaling in chronic inflammatory nociception and neuropathic the opioid peptide tynorphin, which rationalize the enzyme’s sub- pain due to nerve injury (15). strate specificity and reveal an exceptionally large domain motion Tynorphin (Val-Val-Tyr-Pro-Trp), a synthetic, truncated form upon ligand binding. Microcalorimetric analyses point at an en- of spinorphin, is a highly specific inhibitor of DPP III and was tropy-dominated process, with the release of water molecules shown to induce an even more potent antinociceptive effect from the binding cleft (“entropy reservoir”) as the major thermo- (14, 16).
    [Show full text]
  • PRODUCT INFORMATION Spinorphin Item No
    PRODUCT INFORMATION Spinorphin Item No. 29914 NH CAS Registry No.: 137201-62-8 Formal Name: L-leucyl-L-valyl-L-valyl-L-tyrosyl-L- O H O N prolyl-L-tryptophyl-L-threonine N OH O N H Synonyms: Leu-Val-Val-Tyr-Pro-Trp-Thr, O OH H LVVYPWT O O N MF: C45H64N8O10 N N O FW: 877.0 H H NH2 Purity: ≥95% UV/Vis.: λmax: 222 nm Supplied as: A crystalline solid Storage: -20°C OH Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Spinorphin is supplied as a crystalline solid. A stock solution may be made by dissolving the spinorphin in the solvent of choice, which should be purged with an inert gas. Spinorphin is soluble in organic solvents such as DMSO and dimethyl formamide. The solubility of spinorphin in these solvents is approximately 30 mg/ml. Description Spinorphin is a heptapeptide inhibitor of the enkephalin-degrading enzymes aminopeptidase, dipeptidyl aminopeptidase, angiotensin-converting enzyme (ACE), and enkephalinase (IC50s = 3.3, 1.4, 2.4, and 10 µg/ml, respectively, for monkey brain enzymes).1 It is selective for these enzymes over human serum aminopeptidase A (IC50 = >100 µg/ml), as well as porcine kidney aminopeptidase B, aminopeptidase M, dipeptidyl peptidase 1 (DPP-1), DPP-2, DPP-3, and DPP-4 (IC50s = >55 µg/ml for all). Spinorphin inhibits chemotaxis, production of reactive oxygen species (ROS), and exocytosis of glucuronidase and collagenase in polymorphonuclear neutrophils (PMNs). It potentiates enkephalin-induced action potentials in rat hippocampal slices.
    [Show full text]
  • 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]
  • Biased Signaling by Endogenous Opioid Peptides
    Biased signaling by endogenous opioid peptides Ivone Gomesa, Salvador Sierrab,1, Lindsay Lueptowc,1, Achla Guptaa,1, Shawn Goutyd, Elyssa B. Margolise, Brian M. Coxd, and Lakshmi A. Devia,2 aDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; bDepartment of Physiology & Biophysics, Virginia Commonwealth University, Richmond, VA 23298; cSemel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095; dDepartment of Pharmacology & Molecular Therapeutics, Uniformed Services University, Bethesda MD 20814; and eDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94143 Edited by Susan G. Amara, National Institutes of Health, Bethesda, MD, and approved April 14, 2020 (received for review January 20, 2020) Opioids, such as morphine and fentanyl, are widely used for the possibility that endogenous opioid peptides could vary in this treatment of severe pain; however, prolonged treatment with manner as well (13). these drugs leads to the development of tolerance and can lead to For opioid receptors, studies showed that mice lacking opioid use disorder. The “Opioid Epidemic” has generated a drive β-arrestin2 exhibited enhanced and prolonged morphine-mediated for a deeper understanding of the fundamental signaling mecha- antinociception, and a reduction in side-effects, such as devel- nisms of opioid receptors. It is generally thought that the three opment of tolerance and acute constipation (15, 16). This led to types of opioid receptors (μ, δ, κ) are activated by endogenous studies examining whether μOR agonists exhibit biased signaling peptides derived from three different precursors: Proopiomelano- (17–20), and to the identification of agonists that preferentially cortin, proenkephalin, and prodynorphin.
    [Show full text]
  • A 0.70% E 0.80% Is 0.90%
    US 20080317666A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0317666 A1 Fattal et al. (43) Pub. Date: Dec. 25, 2008 (54) COLONIC DELIVERY OF ACTIVE AGENTS Publication Classification (51) Int. Cl. (76) Inventors: Elias Fattal, Paris (FR); Antoine A6IR 9/00 (2006.01) Andremont, Malakoff (FR); A61R 49/00 (2006.01) Patrick Couvreur, A6II 5L/12 (2006.01) Villebon-sur-Yvette (FR); Sandrine A6IPI/00 (2006.01) Bourgeois, Lyon (FR) (52) U.S. Cl. .......................... 424/1.11; 424/423; 424/9.1 (57) ABSTRACT Correspondence Address: Drug delivery devices that are orally administered, and that David S. Bradlin release active ingredients in the colon, are disclosed. In one Womble Carlyle Sandridge & Rice embodiment, the active ingredients are those that inactivate P.O.BOX 7037 antibiotics, such as macrollides, quinolones and beta-lactam Atlanta, GA 30359-0037 (US) containing antibiotics. One example of a Suitable active agent is an enzyme Such as beta-lactamases. In another embodi ment, the active agents are those that specifically treat colonic (21) Appl. No.: 11/628,832 disorders, such as Chrohn's Disease, irritable bowel syn drome, ulcerative colitis, colorectal cancer or constipation. (22) PCT Filed: Feb. 9, 2006 The drug delivery devices are in the form of beads of pectin, crosslinked with calcium and reticulated with polyethylene imine. The high crosslink density of the polyethyleneimine is (86). PCT No.: PCT/GBO6/OO448 believed to stabilize the pectin beads for a sufficient amount of time such that a Substantial amount of the active ingredi S371 (c)(1), ents can be administered directly to the colon.
    [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]
  • 251-Bolton-Hunter- Labeled Substance P Binding Sites in Rat Spinal Cord’
    0270.6474/65/0505-1293$02.00/O The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 5, No. 5, pp. 1293-1299 Printed in U.S.A. May 1985 Characterization and Segmental Distribution of ‘251-Bolton-Hunter- labeled Substance P Binding Sites in Rat Spinal Cord’ CLIVEL G. CHARLTON’ AND CINDA J. HELKE Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 Abstract al., 1982) are two sources for SP in the ventral horn. The nucleus interfascicularis hypoglossi also supplies SP-containing nerve termi- Substance P (SP) is widely distributed in the spinal cord nals to the IML cells of origin for autonomic preganglion fibers (Helke and has been implicated as a neurotransmitter in several et al., 1982). spinal cord neuronal systems. To investigate SP receptors in Functional studies support the concept of a neurotransmOitter role the spinal cord, 1251-Bolton-Hunter-SP (‘*‘I-BH-SP) was used for SP in the spinal cord. Nociception (Piercey et al., 1981; Akerman to identify and characterize spinal cord binding sites for the et al., 1982; Fasmer and Post, 1983) motor control (Otsuka and peptide. The binding of ‘*%BH-SP had the following charac- Konishi, 1977; Yanagisawa et al., 1982) and certain autonomic teristics: high affinity; time, temperature, and membrane con- functions (Loewy and Sawyer, 1982; Keeler and Helke, 1984) are centration dependent; reversible; and saturable. The KS0 of modulated by spinal cord SP. In addition, SP receptors in the spinal SP in whole spinal cord was 0.46 nM as compared with 0.95, cord have been demonstrated by iontophoretic studies in which SP 60, and 150 nM for physalaemin, eledoisin, and kassinin.
    [Show full text]
  • Formylpeptide Receptor N Antagonist at The
    The Endogenous Opioid Spinorphin Blocks fMet-Leu-Phe-Induced Neutrophil Chemotaxis by Acting as a Specific Antagonist at the N-Formylpeptide Receptor This information is current as Subtype FPR of October 1, 2021. Thomas S. Liang, Ji-Liang Gao, Omid Fatemi, Mark Lavigne, Thomas L. Leto and Philip M. Murphy J Immunol 2001; 167:6609-6614; ; doi: 10.4049/jimmunol.167.11.6609 Downloaded from http://www.jimmunol.org/content/167/11/6609 References This article cites 48 articles, 13 of which you can access for free at: http://www.jimmunol.org/content/167/11/6609.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Endogenous Opioid Spinorphin Blocks fMet-Leu-Phe-Induced Neutrophil Chemotaxis by Acting as a Specific Antagonist at the N-Formylpeptide Receptor Subtype FPR Thomas S.
    [Show full text]
  • G Protein-Coupled Receptors
    S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. British Journal of Pharmacology (2015) 172, 5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors Stephen PH Alexander1, Anthony P Davenport2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5 and CGTP Collaborators 1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, 2Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/ 10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading.
    [Show full text]