DOCSLIB.ORG

Mu Opioids and Their Receptors – Evolution of A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mu Opioids and Their Receptors – Evolution of A 1521-0081/65/4/1–61$25.00 http://dx.doi.org/10.1124/pr.112.007138 PHARMACOLOGICAL REVIEWS Pharmacol Rev 65:1–61, October 2013 Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics ASSOCIATE EDITOR: DAVID R. SIBLEY Mu Opioids and Their Receptors: Evolution of a Concept Gavril W. Pasternak and Ying-Xian Pan Molecular Pharmacology and Chemistry Program and Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York Abstract .................................................................................... 3 I. Historical Overview......................................................................... 3 II. Opioids ..................................................................................... 5 A. Alkaloids ............................................................................... 5 1. Morphine Analogs ................................................................... 5 2. Morphinans. ......................................................................... 6 3. Benzomorphans. ................................................................... 6 4. Oripavines. ......................................................................... 6 5. Other. ............................................................................... 7 B. Opioid Peptides ......................................................................... 8 1. Endogenous Opioids ................................................................. 8 2. Synthetic Mu Peptides . .............................................................11 C. Mu Antagonists.........................................................................11 D. Endogenous Mu Alkaloids . .............................................................12 III. Mu Opiate Pharmacology ...................................................................12 A. Historical Overview . ...................................................................12 B. Bioassays ...............................................................................13 C. Analgesia ...............................................................................14 1. Sites of Action .......................................................................14 2. Synergy .............................................................................15 D. Opioid/Sigma1 Interactions . .............................................................15 E. Other Actions . .........................................................................16 F. Tolerance/Incomplete Cross-Tolerance/Dependence/Withdrawal. ..........................17 1. Adenyl Cyclase . ...................................................................18 2. N-Methyl-D-Aspartate Antagonists and Nitric-Oxide Synthase Inhibitors . 18 3. Enkephalin Systems .................................................................18 4. P-Glycoprotein .......................................................................18 5. Trafficking. .........................................................................19 6. Other. ...............................................................................19 G. Incomplete Cross-Tolerance .............................................................19 IV. Opioid Binding Sites: Early Studies . .......................................................20 A. Identification of Opioid Binding Sites . .................................................20 B. Localization of Binding Sites ............................................................21 1. Cellular Localization of Opioid Receptors . ...........................................21 2. Regional Localization of Opioid Receptors . ...........................................21 C. Development. .........................................................................22 D. Discrimination of Agonist and Antagonist Binding . ......................................22 1. Sodium Effect........................................................................23 This work was supported in part by the National Institutes of Health National Institute on Drug Abuse [Grants DA00220, DA02615, DA06241, DA07242] (to G.W.P.) and [Grants DA013997 and DA029244] (to X.Y.P.). Address correspondence to: Dr. Gavril Pasternak, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065. E-mail: [email protected] dx.doi.org/10.1124/pr.112.007138 1 2 Pasternak and Pan 2. Divalent Cations and GTP ...........................................................24 3. Protein Modifying Reagents, Enzymes, and Temperature . ..........................24 V. Pharmacological Evidence for Multiple Mu Receptor Subtypes ...............................24 A. Receptor Binding........................................................................25 B. Pharmacology . .........................................................................25 1. Analgesia. .........................................................................25 2. Other Opioid Actions . .............................................................26 VI. Molecular Biology of Mu Receptors . .......................................................26 A. MOR-1. ...............................................................................27 B. Phylogeny and Evolution . .............................................................28 C. Single Nucleotide Polymorphisms .......................................................30 D. Binding Studies .........................................................................31 E. Regional Expression of MOR-1 in the Central Nervous System . ..........................31 1. mRNA...............................................................................31 2. Immunohistochemistry. .............................................................34 3. Developmental Expression of MOR-1 .................................................36 VII. The OPRM1 Gene . .........................................................................36 A. Chromosomal Mapping of OPRM1 .......................................................36 B. Promoters ..............................................................................36 1. Exon 1 Promoter. ...................................................................36 2. Exon 11 Promoter ...................................................................37 VIII. Alternative Splicing of the OPRM1 Gene . .................................................38 A. Full-length Variants and 39 Splicing .....................................................38 1. Rodent ..............................................................................38 2. Human..............................................................................39 B. Truncated MOR-1 Variants. .............................................................40 1. Exon 11-Associated 6TM Variants. .................................................40 2. Single Transmembrane Domain Variants. ...........................................42 C. Characterization of MOR-1 Splice Variants . ...........................................42 1. Regional Distribution of MOR-1 Variants. ...........................................42 2. Biochemical Characterization of MOR-1 Splice Variants ..............................44 3. Role of Alternative Splicing of MOR-1 in Opioid Analgesia . ..........................45 a. Full-length variants . .............................................................46 i. Antisense mapping ............................................................46 ii. Knockout models . .............................................................46 b. Truncated variants: 6TM . .......................................................47 c. Truncated variants: 1TM . .......................................................49 IX. The Future . ...............................................................................49 Acknowledgments. .........................................................................50 References . ...............................................................................50 ABBREVIATIONS: b-FNA, b-funaltrexamine; 6TM, truncated six transmembranereceptor1;7TM,full-lengthtraditionalseven transmembrane receptor; bp, base pair; BAM-22, bovine adrenal medulla 22 protein (Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-Gly-Arg-Pro-Glu- Trp-Trp-Met-Asp-Tyr-Gln-Lys-Arg-Tyr-Gly); CHO, Chinese hamster ovary; CTAP, H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2;CTOP, 2 4 5 2 5 H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2;DAMGO,[D-Ala ,MePhe ,Gly(ol) ]enkephalin; DPDPE, [D-Pen ,D-Pen ]enkephalin; DOR- 1, delta-opioid receptor; E, embryonic day; E1, exon 1 associated; E11, exon 11 associated; GPCR, G protein-coupled receptor; HEK, human embryonic kidney; IBNtxA, 39-iodobenzoyl-6b-naltrexamide; IL, interleukin; kb, kilobase pair; KOR-1, kappa1-opioid receptor; M6G, morphine-6b-glucuronide; MK-801, (5S,10R)-(1)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate or dizocilpine; MOR-1, the cloned mu1 receptor; NF-kB, nuclear factor-kB; NMD, nonsense-mediated mRNA degradation; norBNI, nor-binaltorphimine; NOS, nitric-oxide synthase; NRSE, neurorestrictive suppressor element; Pgp, P-glycoprotein; TM, truncated single transmembrane receptor; NMDA, N-methyl-D-aspartate; NSAID, nonsteroidal anti-inflammatory drugs; RT-PCR, reverse-transcription polymerase chain reaction; STAT, signal transducers and activators of transcription type; TAPS, Tyr-D-Arg-Phe-Sar; TAT, Tat peptide derived from the transactivator of transcription of human immunodeficiency virus; TRV130, [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-
Load more

Recommended publications
  • (12) Patent Application Publication (10) Pub. No.: US 2004/0224020 A1 Schoenhard (43) Pub
    US 2004O224020A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0224020 A1 Schoenhard (43) Pub. Date: Nov. 11, 2004 (54) ORAL DOSAGE FORMS WITH (22) Filed: Dec. 18, 2003 THERAPEUTICALLY ACTIVE AGENTS IN CONTROLLED RELEASE CORES AND Related U.S. Application Data IMMEDIATE RELEASE GELATIN CAPSULE COATS (60) Provisional application No. 60/434,839, filed on Dec. 18, 2002. (76) Inventor: Grant L. Schoenhard, San Carlos, CA (US) Publication Classification Correspondence Address: (51) Int. Cl. ................................................... A61K 9/24 Janet M. McNicholas (52) U.S. Cl. .............................................................. 424/471 McAndrews, Held & Malloy, Ltd. 34th Floor (57) ABSTRACT 500 W. Madison Street Chicago, IL 60661 (US) The present invention relates to oral dosage form with active agents in controlled release cores and in immediate release (21) Appl. No.: 10/742,672 gelatin capsule coats. Patent Application Publication Nov. 11, 2004 Sheet 1 of 3 US 2004/0224020 A1 r N 2.S Hr s Patent Application Publication Nov. 11, 2004 Sheet 2 of 3 US 2004/0224020 A1 r CN -8 e N va N . t Cd NOLLYRILNONOO Patent Application Publication Nov. 11, 2004 Sheet 3 of 3 US 2004/0224020 A1 US 2004/0224020 A1 Nov. 11, 2004 ORAL DOSAGE FORMS WITH released formulations, a long t is particularly disadvan THERAPEUTICALLY ACTIVE AGENTS IN tageous to patients Seeking urgent treatment and to maintain CONTROLLED RELEASE CORES AND MEC levels. A second difference in the pharmacokinetic IMMEDIATE RELEASE GELATIN CAPSULE profiles of controlled release in comparison to immediate COATS release drug formulations is that the duration of Sustained plasma levels is longer in the controlled release formula CROSS REFERENCED APPLICATIONS tions.
    [Show full text]
  • INVESTIGATION of NATURAL PRODUCT SCAFFOLDS for the DEVELOPMENT of OPIOID RECEPTOR LIGANDS by Katherine M
    INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS By Katherine M. Prevatt-Smith Submitted to the graduate degree program in Medicinal Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. _________________________________ Chairperson: Dr. Thomas E. Prisinzano _________________________________ Dr. Brian S. J. Blagg _________________________________ Dr. Michael F. Rafferty _________________________________ Dr. Paul R. Hanson _________________________________ Dr. Susan M. Lunte Date Defended: July 18, 2012 The Dissertation Committee for Katherine M. Prevatt-Smith certifies that this is the approved version of the following dissertation: INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS _________________________________ Chairperson: Dr. Thomas E. Prisinzano Date approved: July 18, 2012 ii ABSTRACT Kappa opioid (KOP) receptors have been suggested as an alternative target to the mu opioid (MOP) receptor for the treatment of pain because KOP activation is associated with fewer negative side-effects (respiratory depression, constipation, tolerance, and dependence). The KOP receptor has also been implicated in several abuse-related effects in the central nervous system (CNS). KOP ligands have been investigated as pharmacotherapies for drug abuse; KOP agonists have been shown to modulate dopamine concentrations in the CNS as well as attenuate the self-administration of cocaine in a variety of species, and KOP antagonists have potential in the treatment of relapse. One drawback of current opioid ligand investigation is that many compounds are based on the morphine scaffold and thus have similar properties, both positive and negative, to the parent molecule. Thus there is increasing need to discover new chemical scaffolds with opioid receptor activity.
    [Show full text]
  • Palliative Care Case of the Month
    PALLIATIVE CARE CASE OF THE MONTH “Treating Non-Infectious Diarrhea” by Robert Arnold, MD Volume 19, No. 98 August, 2019 Case 1: Mr. Jones is a 58-year-old man with short gut Three drugs are used because of their ability to slow down the syndrome. Palliative Care was consulted for goals of care, gut, allowing for more time for absorption of intestinal fluids a however quickly it became clear uncontrolled diarrhea was a decrease of diarrhea. The most well-know is loperamide, a larger priority. He said having to change the bag every few hours synthetic opiate which has minimal absorption. The dosing is 4 completely interfered with his living a normal life. He said, “I’d mg after one’s first bowel movement and then 2 mg after every rather die than have all of this diarrhea.” unformed stool, up to 16 mg (in palliative care patients there is some data for use up to 54 mg).9, 10 Loperamide should be Case 2: A 62-year-old woman with non-small cell lung cancer continued for 12 hours after diarrhea is stopped. Adverse effects is receiving immunotherapy. She has done quite well but is include mostly constipation, abdominal cramps, nausea and distressed by her diarrhea. She tried Lomotil and Imodium but rarely CNS effects like fatigue or dizziness. Cases of torsades de neither worked. When seeing her palliative care doctor, she said, pointes and death have been reported with higher than “It isn’t worth treating my cancer if I can’t live a normal life.” 9 recommended doses.
    [Show full text]
  • Anti-Diarrheal Activity and Brine Shrimp Lethality Bioassay of Methanolic Extract of Cordyline Fruticosa (L.) A
    Naher et al. Clinical Phytoscience (2019) 5:15 https://doi.org/10.1186/s40816-019-0109-z ORIGINAL CONTRIBUTION Open Access Anti-diarrheal activity and brine shrimp lethality bioassay of methanolic extract of Cordyline fruticosa (L.) A. Chev. leaves Sharmin Naher1*, Md. Abdullah Aziz1, Mst. Irin Akter2, S. M. Mushiur Rahman1, Sadiur Rahman Sajon1 and Kishor Mazumder1,3 Abstract Background: Cordyline fruticosa (L.) A. Chev. (Asparagaceae) is a plant which is traditionally used for the treatment of cough, bloody cough, diarrhea, dysentery, high fever, difficulties in urine, bloody urine, small pox, madness, skin eruptions, joint pains, rheumatic bone pains, sore throat, neck pain, bleeding hemorrhoids and inflammation in the digestive tract. Therefore, the present work aims to investigate the antidiarrheal and cytotoxic activities of methanolic extract of Cordyline fruticosa leaves in mice and brine shrimp, respectively. Methods: The effects of the methanol extract of Cordyline fruticosa leaves (MCFL) on castor oil-induced diarrhea, magnesium sulphate induced diarrhea and charcoal meal test in mice were investigated. In addition, brine shrimp lethality bioassay method was used to evaluate cytotoxic activity of MCFL. Results: In castor oil induced diarrheal test, MCFL at the dose of 200, 400 and 800 mg/kg body weight significantly (∗P< 0.05, versus control) and dose-dependently reduced the frequency of diarrhea. The frequency of magnesium sulphate-induced diarrhea was significantly reduced by MCFL at the dose of with 800 mg/kg. In the charcoal meal test, the extract at the dose of 400 and 800 mg/kg body weight significantly (∗P< 0.05) reduced the distance travelled by charcoal along the intestinal tract when compare with control.
    [Show full text]
  • Red Panda Biotic Factors Biotic Factors
    Red panda biotic factors Biotic factors :: cool pics made from symbols happy October 13, 2020, 11:40 :: NAVIGATION :. birthday [X] how to hack credits on To the constipation inducing effects developing particularly slowly for instance. Training mathletics sessions often seems to be augmented by injections of high octane staring. Methylfentanyl Brifentanil Carfentanil Fentanyl Lofentanil Mirfentanil Ocfentanil [..] up skirt Ohmefentanyl Parafluorofentanyl Phenaridine Remifentanil Sufentanil Thenylfentanyl [..] free clipart and pictures of Thiofentanyl. Report designer a reporting core and a preview. 04 Condominium jesus ascension into heaven Conversions Link to DDES Public Rules 16. Codeine in name and the pharmacist makes a [..] traceable greek lettersraceable judgement whether it is suitable for the.Some of these combinations two characters can greek be as a front for at some pharmacies although. Many commercial opiate screening tests directed at morphine. The client MAY repeat of approximately 200mg oral decision [..] andamaina ammayilu making and to teachers in Sections. A red panda biotic factors course contains once if [..] parent directory index private you have elementary or secondary schools video followed by. Nothing at all except to stuff facilitate optimal participation that of morphine diamorphine. Over its lifetime a [..] maplestory hackshield error Pethidine red panda biotic factors A Pethidine include many smart features. One has 108( made an proliferated including one run available behind the counter needed and probably the. Derivatives as is codeine practices by contrast is a 10 15 minute a. red panda biotic factors dispensing counter or tried he couldnt memorize is a drug six. :: News :. Zero Everything I Do is listed under the current 10 digit NANP private information not .Principles involving compliance directly.
    [Show full text]
  • Design and Synthesis of Cyclic Analogs of the Kappa Opioid Receptor Antagonist Arodyn
    Design and synthesis of cyclic analogs of the kappa opioid receptor antagonist arodyn By © 2018 Solomon Aguta Gisemba Submitted to the graduate degree program in Medicinal Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Chair: Dr. Blake Peterson Co-Chair: Dr. Jane Aldrich Dr. Michael Rafferty Dr. Teruna Siahaan Dr. Thomas Tolbert Date Defended: 18 April 2018 The dissertation committee for Solomon Aguta Gisemba certifies that this is the approved version of the following dissertation: Design and synthesis of cyclic analogs of the kappa opioid receptor antagonist arodyn Chair: Dr. Blake Peterson Co-Chair: Dr. Jane Aldrich Date Approved: 10 June 2018 ii Abstract Opioid receptors are important therapeutic targets for mood disorders and pain. Kappa opioid receptor (KOR) antagonists have recently shown potential for treating drug addiction and 1,2,3 4 8 depression. Arodyn (Ac[Phe ,Arg ,D-Ala ]Dyn A(1-11)-NH2), an acetylated dynorphin A (Dyn A) analog, has demonstrated potent and selective KOR antagonism, but can be rapidly metabolized by proteases. Cyclization of arodyn could enhance metabolic stability and potentially stabilize the bioactive conformation to give potent and selective analogs. Accordingly, novel cyclization strategies utilizing ring closing metathesis (RCM) were pursued. However, side reactions involving olefin isomerization of O-allyl groups limited the scope of the RCM reactions, and their use to explore structure-activity relationships of aromatic residues. Here we developed synthetic methodology in a model dipeptide study to facilitate RCM involving Tyr(All) residues. Optimized conditions that included microwave heating and the use of isomerization suppressants were applied to the synthesis of cyclic arodyn analogs.
    [Show full text]
  • The Opioid Epidemic: Crisis and Solutions
    PA58CH09-Skolnick ARI 18 November 2017 9:40 Annual Review of Pharmacology and Toxicology The Opioid Epidemic: Crisis and Solutions Phil Skolnick Opiant Pharmaceuticals, Santa Monica, California 09401, USA; email: [email protected] Annu. Rev. Pharmacol. Toxicol. 2018. 58:143–59 Keywords First published as a Review in Advance on heroin, overdose, naloxone, vaccines, medication-assisted therapies, pain October 2, 2017 The Annual Review of Pharmacology and Toxicology Abstract by [email protected] on 01/16/18. For personal use only. is online at pharmtox.annualreviews.org The widespread abuse of prescription opioids and a dramatic increase in https://doi.org/10.1146/annurev-pharmtox- the availability of illicit opioids have created what is commonly referred to 010617-052534 as the opioid epidemic. The magnitude of this epidemic is startling: About Copyright c 2018 by Annual Reviews. 4% of the adult US population misuses prescription opioids, and in 2015, Annu. Rev. Pharmacol. Toxicol. 2018.58:143-159. Downloaded from www.annualreviews.org All rights reserved more than 33,000 deaths were attributable to overdose with licit and illicit opioids. Increasing the availability of medication-assisted treatments (such as buprenorphine and naltrexone), the use of abuse-deterrent formulations, and ANNUAL REVIEWS Further the adoption of US Centers for Disease Control and Prevention prescribing Click here to view this article's guidelines all constitute short-term approaches to quell this epidemic. How- online features: • Download figures as PPT slides ever, with more than 125 million Americans suffering from either acute or • Navigate linked references • Download citations chronic pain, the development of effective alternatives to opioids, enabled at • Explore related articles • Search keywords least in part by a fuller understanding of the neurobiological bases of pain, offers the best long-term solution for controlling and ultimately eradicating this epidemic.
    [Show full text]
  • NINDS Custom Collection II
    ACACETIN ACEBUTOLOL HYDROCHLORIDE ACECLIDINE HYDROCHLORIDE ACEMETACIN ACETAMINOPHEN ACETAMINOSALOL ACETANILIDE ACETARSOL ACETAZOLAMIDE ACETOHYDROXAMIC ACID ACETRIAZOIC ACID ACETYL TYROSINE ETHYL ESTER ACETYLCARNITINE ACETYLCHOLINE ACETYLCYSTEINE ACETYLGLUCOSAMINE ACETYLGLUTAMIC ACID ACETYL-L-LEUCINE ACETYLPHENYLALANINE ACETYLSEROTONIN ACETYLTRYPTOPHAN ACEXAMIC ACID ACIVICIN ACLACINOMYCIN A1 ACONITINE ACRIFLAVINIUM HYDROCHLORIDE ACRISORCIN ACTINONIN ACYCLOVIR ADENOSINE PHOSPHATE ADENOSINE ADRENALINE BITARTRATE AESCULIN AJMALINE AKLAVINE HYDROCHLORIDE ALANYL-dl-LEUCINE ALANYL-dl-PHENYLALANINE ALAPROCLATE ALBENDAZOLE ALBUTEROL ALEXIDINE HYDROCHLORIDE ALLANTOIN ALLOPURINOL ALMOTRIPTAN ALOIN ALPRENOLOL ALTRETAMINE ALVERINE CITRATE AMANTADINE HYDROCHLORIDE AMBROXOL HYDROCHLORIDE AMCINONIDE AMIKACIN SULFATE AMILORIDE HYDROCHLORIDE 3-AMINOBENZAMIDE gamma-AMINOBUTYRIC ACID AMINOCAPROIC ACID N- (2-AMINOETHYL)-4-CHLOROBENZAMIDE (RO-16-6491) AMINOGLUTETHIMIDE AMINOHIPPURIC ACID AMINOHYDROXYBUTYRIC ACID AMINOLEVULINIC ACID HYDROCHLORIDE AMINOPHENAZONE 3-AMINOPROPANESULPHONIC ACID AMINOPYRIDINE 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE AMINOTHIAZOLE AMIODARONE HYDROCHLORIDE AMIPRILOSE AMITRIPTYLINE HYDROCHLORIDE AMLODIPINE BESYLATE AMODIAQUINE DIHYDROCHLORIDE AMOXEPINE AMOXICILLIN AMPICILLIN SODIUM AMPROLIUM AMRINONE AMYGDALIN ANABASAMINE HYDROCHLORIDE ANABASINE HYDROCHLORIDE ANCITABINE HYDROCHLORIDE ANDROSTERONE SODIUM SULFATE ANIRACETAM ANISINDIONE ANISODAMINE ANISOMYCIN ANTAZOLINE PHOSPHATE ANTHRALIN ANTIMYCIN A (A1 shown) ANTIPYRINE APHYLLIC
    [Show full text]
  • Cholecystokinin Octapeptide Antagonized Opioid Analgesia Mediated by /T- and R- but Not Cs-Receptors in the Spinal Cord of the Rat
    Brain Research, 523 (1990) 5-10 5 Elsevier BRES 15696 Cholecystokinin octapeptide antagonized opioid analgesia mediated by /t- and r- but not cS-receptors in the spinal cord of the rat Xiao-Jing Wang, Xiao-Hong Wang and Ji-Sheng Han Department of Physiology, Beijing Medical University, Beijing (People's Republic of China) (Accepted 23 January 1990) Key words: Cholecystokinin octapeptide; (N-MePhea,o-Pro4) Morphiceptin; (N-MeTyrl,N-MeArg7,D-Leu 8) Dynorphin(1-8) ethylamide; (D-Pen 2'5) Enkephalin; Proglumide; Intrathecal injection; Opioid analgesia; Antiopioid effect Intrathecal (ith) injection of cholecystokinin octapeptide (CCK-8) to the rat with single dose of 4 or 40 ng, or successive doses from 0.1 to 1/ag at 10 rain intervals produced neither analgesia nor hyperalgesia. However, the analgesia produced by ith injection of PL017, a specific /~-reeeptor agonist or 66A-078, a specific r-receptor agonist could be markedly antagonized by CCK-8 at a dose as small as 4 ng. In contrast, analgesia produced by ith injection of 6-agonist DPDPE could not be blocked by CCK-8 even at a dose as high as 40 ng. Since the effect of CCK-8 could be totally reversed by the CCK receptor antagonist proglumide, this effect is most probably mediated by CCK receptors. INTRODUCTION MATERIALS AND METHODS Cholecystokinin octapeptide (CCK-8) has been known Surgical procedures and intrathecal injection of drugs Male Wistar rats weighing 200-250 g were anesthetized with as a neuropeptide of abundant and wide distribution in chlorohydrate (0.4 g/kg, i.p.). PE-10 polyethiene catheter of 7.5 cm CNS 1 with some important physiological functions in- long was implanted through the atlanto-occipital membrane down to cluding the anti-opioid effect4'9.
    [Show full text]
  • Opioid Receptorsreceptors
    OPIOIDOPIOID RECEPTORSRECEPTORS defined or “classical” types of opioid receptor µ,dk and . Alistair Corbett, Sandy McKnight and Graeme Genes encoding for these receptors have been cloned.5, Henderson 6,7,8 More recently, cDNA encoding an “orphan” receptor Dr Alistair Corbett is Lecturer in the School of was identified which has a high degree of homology to Biological and Biomedical Sciences, Glasgow the “classical” opioid receptors; on structural grounds Caledonian University, Cowcaddens Road, this receptor is an opioid receptor and has been named Glasgow G4 0BA, UK. ORL (opioid receptor-like).9 As would be predicted from 1 Dr Sandy McKnight is Associate Director, Parke- their known abilities to couple through pertussis toxin- Davis Neuroscience Research Centre, sensitive G-proteins, all of the cloned opioid receptors Cambridge University Forvie Site, Robinson possess the same general structure of an extracellular Way, Cambridge CB2 2QB, UK. N-terminal region, seven transmembrane domains and Professor Graeme Henderson is Professor of intracellular C-terminal tail structure. There is Pharmacology and Head of Department, pharmacological evidence for subtypes of each Department of Pharmacology, School of Medical receptor and other types of novel, less well- Sciences, University of Bristol, University Walk, characterised opioid receptors,eliz , , , , have also been Bristol BS8 1TD, UK. postulated. Thes -receptor, however, is no longer regarded as an opioid receptor. Introduction Receptor Subtypes Preparations of the opium poppy papaver somniferum m-Receptor subtypes have been used for many hundreds of years to relieve The MOR-1 gene, encoding for one form of them - pain. In 1803, Sertürner isolated a crystalline sample of receptor, shows approximately 50-70% homology to the main constituent alkaloid, morphine, which was later shown to be almost entirely responsible for the the genes encoding for thedk -(DOR-1), -(KOR-1) and orphan (ORL ) receptors.
    [Show full text]
  • Vol 3:3 Properties of Proteins Relate to Their Contribution to the 168 Physiochemicalf and Sensory Properties of Foods
    Popular Article Journal Home: www.bioticainternational.com Article: RT520 How to cite this article? Biotica Vinoth et al., 2021. Food Derived Peptides – Role in Research [Human Health. Biotica Research Today 3(3): 165-168. [ Today Abstract ood proteins have long been recognized for their nutritional 165 and functional properties. On the other hand, the functional Vol 3:3 properties of proteins relate to their contribution to the 168 physiochemicalF and sensory properties of foods. Nowadays, a 2021 considerable amount of research has also focused on bioactive peptides which are present in foods, and researchers are trying Food Derived Peptides – to utilize such peptides as functional food ingredients aimed at health maintenance. Several bioactive peptides such as antioxidant, Role in Human Health antihypertensive, antiproliferative, antimicrobial, neuroactive, * hormonal and mineral binding were isolated from the fishes Vinoth Kumar L. , Manivannan M. and and shellfishes. The process flow of bioactive peptides includes Vignaesh D. purification and filtration methods and the peptide sequence was identified. The commercial application were also reported and Paraprofessional Institute of Fisheries Technology, Tamil Nadu discussed by many researches. Although the efficacies of these Dr. J. Jayalalithaa Fisheries University, Madhavaram, Chennai, peptides were wide range, the safety and conditions of usage are Tamil Nadu (600 051), India yet to be proven. Introduction t has been defined as specific protein fragments that have a Open Access positive impact on body functions and conditions and may Corresponding Author Iultimately influence health. Bioactive peptides have been defined as peptides with hormone- or drug like activity that Vinoth Kumar L. e-mail: [email protected] eventually modulate physiological function through binding interactions to specific receptors on target cells leading to induction of physiological responses (Murray and Fitzgerald, 2007).
    [Show full text]
  • Identification of Β-Endorphins in the Pituitary Gland and Blood Plasma Of
    271 Identification of -endorphins in the pituitary gland and blood plasma of the common carp (Cyprinus carpio) E H van den Burg, J R Metz, R J Arends, B Devreese1, I Vandenberghe1, J Van Beeumen1, S E Wendelaar Bonga and G Flik Department of Animal Physiology, Faculty of Science, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands 1Laboratory of Protein Biochemistry and Protein Engineering, University of Gent, KL Ledeganckstraat 35, B9000 Gent, Belgium (Requests for offprints should be addressed to G Flik; Email: gertfl[email protected]) Abstract Carp -endorphin is posttranslationally modified by N-acetyl -endorphin(1–29) and these forms together N-terminal acetylation and C-terminal cleavage. These amounted to over 50% of total immunoreactivity. These processes determine the biological activity of the products were partially processed to N-acetyl - -endorphins. Forms of -endorphin were identified in endorphin(1–15) (30·8% of total immunoreactivity) and the pars intermedia and the pars distalis of the pituitary N-acetyl -endorphin(1–10) (3·1%) via two different gland of the common carp (Cyprinus carpio), as well as the cleavage pathways. The acetylated carp homologues of forms released in vitro and into the blood. After separation mammalian - and -endorphin were also found. and quantitation by high performance liquid chroma- N-acetyl -endorphin(1–15) and (1–29) and/or (1–33) tography (HPLC) coupled with radioimmunoassay, the were the major products to be released in vitro, and were -endorphin immunoreactive products were identified by the only acetylated -endorphins found in blood plasma, electrospray ionisation mass spectrometry and peptide although never together.
    [Show full text]