Evidence map›Paper›PMID 26947933›Full record

ArticleBritish journal of pharmacology2016

PnPP-19, a spider toxin peptide, induces peripheral antinociception through opioid and cannabinoid receptors and inhibition of neutral endopeptidase.

A C N Freitas, D F Pacheco, M F M Machado, A K Carmona, I D G Duarte, M E de Lima

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

14 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Pain-related toxins in scorpion and spider venoms: a face to face with ion channels.The journal of venomous animals and toxins including tropical diseases · 2021
    Review
  6. Article
  7. Review
  8. Review
  9. Spider venom peptides as potential drug candidates due to their anticancer and antinociceptive activities.The journal of venomous animals and toxins including tropical diseases · 2019
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems.The journal of venomous animals and toxins including tropical diseases · 2016
    Article
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

6 authors at 2 institutions in 1 country.

A C N FreitasDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
D F PachecoDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
M F M MachadoDepartamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
A K CarmonaDepartamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
I D G DuarteDepartamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
M E de LimaDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais · BRUniversidade Federal de São Paulo · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeThe synthetic peptide PnPP-19 has been studied as a new drug candidate to treat erectile dysfunction. However, PnTx2-6, the spider toxin from which the peptide was designed, induces hyperalgesia. Therefore, we intended to investigate the role of PnPP-19 in the nociceptive pathway. EXPERIMENTAL APPROACH: Nociceptive thresholds were measured by paw pressure test. PnPP-19 was administered intraplantarly alone or with selective cannabinoid or opioid receptor antagonists. The hydrolysis of PnPP-19 by neutral endopeptidase (NEP) (EC 3.4.24.11), an enzyme that cleaves enkephalin, was monitored by HPLC and the cleavage sites were deduced by LC-MS. Inhibition by PnPP-19 and Leu-enkephalin of NEP enzyme activity was determined spectrofluorimetrically. KEY

resultsPnPP-19 (5, 10 and 20 μg per paw) induced peripheral antinociception in rats. Specific antagonists of μ opioid receptors (clocinnamox), δ opioid receptors (naltrindole) and CB1 receptors (AM251) partly inhibited the antinociceptive effect of PnPP-19. Inhibition of fatty acid amide hydrolase by MAFP or of anandamide uptake by VDM11 enhanced PnPP-19-induced antinociception. NEP cleaved PnPP-19 only after a long incubation, and Ki values of 35.6 ± 1.4 and 14.6 ± 0.44 μmol·L(-1) were determined for PnPP-19 and Leu-enkephalin respectively as inhibitors of NEP activity. CONCLUSIONS AND IMPLICATIONS: Antinociception induced by PnPP-19 appears to involve the inhibition of NEP and activation of CB1, μ and δ opioid receptors. Our data provide a greater understanding of the antinociceptive effects of PnPP-19. This peptide could be useful as a new antinociceptive drug candidate.

Indexed as

Analgesics, OpioidAnimalsDose-Response Relationship, DrugEnzyme InhibitorsMaleNeprilysinPeptidesRatsRats, WistarReceptor, Cannabinoid, CB1Receptors, OpioidSpider VenomsStructure-Activity RelationshipAnalgesics, OpioidEnzyme InhibitorsNeprilysinPeptidesReceptor, Cannabinoid, CB1Receptors, OpioidSpider Venoms

Identifiers

PMID26947933
PMCPMC4831307
OpenAlexW2295016831

What OpenQuestion holds

Textmetadata
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.