Evidence map›Paper›PMID 26091169›Full record

ArticleChemistry & biology2015

Single Amino Acid Variation Underlies Species-Specific Sensitivity to Amphibian Skin-Derived Opioid-like Peptides.

Eyal Vardy, Maria F Sassano, Andrew J Rennekamp, Wesley K Kroeze, Philip D Mosier, Richard B Westkaemper, Craig W Stevens, Vsevolod Katritch, Raymond C Stevens, Randall T Peterson and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. New Technologies for Elucidating Opioid Receptor Function.Trends in pharmacological sciences · 2016
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

Eyal VardyDepartment of Pharmacology, UNC Chapel Hill Medical School, 4072 Genetic Medicine Building, 120 Mason Farm Road, Chapel Hill, NC 27514, USA.
Maria F SassanoDepartment of Pharmacology, UNC Chapel Hill Medical School, 4072 Genetic Medicine Building, 120 Mason Farm Road, Chapel Hill, NC 27514, USA.
Andrew J RennekampCardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13(th) Street, Charlestown, MA 02129, USA; Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA.
Wesley K KroezeDepartment of Pharmacology, UNC Chapel Hill Medical School, 4072 Genetic Medicine Building, 120 Mason Farm Road, Chapel Hill, NC 27514, USA.
Philip D MosierDepartment of Medicinal Chemistry, Virginia Commonwealth University School of Pharmacy, Richmond, VA 23298, USA.
Richard B WestkaemperDepartment of Medicinal Chemistry, Virginia Commonwealth University School of Pharmacy, Richmond, VA 23298, USA.
Craig W StevensDepartment of Pharmacology & Physiology, Oklahoma State University Center for Health Sciences, 1111 West 17(th) Street, Tulsa, OK 74107, USA.
Vsevolod KatritchDepartment of Biological Sciences and Chemistry, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA.
Raymond C StevensDepartment of Biological Sciences and Chemistry, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA.
Randall T PetersonCardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13(th) Street, Charlestown, MA 02129, USA; Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA.
Bryan L RothDepartment of Pharmacology, UNC Chapel Hill Medical School, 4072 Genetic Medicine Building, 120 Mason Farm Road, Chapel Hill, NC 27514, USA. Electronic address: bryan_roth@med.unc.edu.
University of North Carolina at Chapel Hill · USBroad Institute · USUniversity of Southern California · USVirginia Commonwealth University · USOklahoma State University Center for Health Sciences · US

Funding

Structure-Function of Opioid ReceptorsP01DA035764 · NIDA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEREZOV, VADIM, ROTH, BRYAN L. · 2014 to 2018
$7.1M
Diterpines as Selective Kappa Opioid Receptor AgonistsR01DA017204 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROTH, BRYAN L. · 2003 to 2014
$3.2M
Scalable technologies for illuminating the druggable GPCR-omeU01MH104974 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROTH, BRYAN L., SHOICHET, BRIAN K · 2014 to 2016
$1.4M
Rational discovery of new DOR chemotypes to prevent addiction and overdoseR33DA038858 · NIDA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KATRITCH, VSEVOLOD · 2017 to 2018
$719k
Rational discovery of new DOR chemotypes to prevent addiction and overdoseR21DA038858 · NIDA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KATRITCH, VSEVOLOD · 2015 to 2016
$410k
NIDA NIH HHS P01 DA035764NIDA NIH HHS R01 DA017204NIDA NIH HHS R21 DA038858NIDA NIH HHS R33 DA038858NIMH NIH HHS HHSN271201300017CNIMH NIH HHS U01 MH104974
6 · The paper itself

Abstract

It has been suggested that the evolution of vertebrate opioid receptors (ORs) follow a vector of increased functionality. Here, we test this idea by comparing human and frog ORs. Interestingly, some of the most potent opioid peptides known have been isolated from amphibian skin secretions. Here we show that such peptides (dermorphin and deltorphin) are highly potent in the human receptors and inactive in frog ORs. The molecular basis for the insensitivity of the frog ORs to these peptides was studied using chimeras and molecular modeling. The insensitivity of the delta OR (DOR) to deltorphin was due to variation of a single amino acid, Trp7.35, which is a leucine in mammalian DORs. Notably, Trp7.35 is completely conserved in all known DOR sequences from lamprey, fish, and amphibians. The deltorphin-insensitive phenotype was verified in fish. Our results provide a molecular explanation for the species selectivity of skin-derived opioid peptides.

Indexed as

Amino Acid SequenceAmphibiansAnalgesics, OpioidAnimalsBehavior, AnimalBinding SitesHumansKineticsMolecular Dynamics SimulationMolecular Sequence DataOligopeptidesOpioid PeptidesPeptidesProtein Structure, TertiaryReceptors, OpioidSequence AlignmentAnalgesics, OpioiddeltorphindermorphinOligopeptidesOpioid PeptidesPeptidesReceptors, Opioid

Identifiers

PMID26091169
PMCPMC4507497
OpenAlexW1593747951

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.