Evidence map›Paper›PMID 24047499›Full record

ArticleCell communication and signaling : CCS2013

Bradykinin-induced Ca2+ signaling in human subcutaneous fibroblasts involves ATP release via hemichannels leading to P2Y12 receptors activation.

Ana Rita Pinheiro, Diogo Paramos-de-Carvalho, Mariana Certal, Cristina Costa, Maria Teresa Magalhães-Cardoso, Fátima Ferreirinha, Maria Adelina Costa, Paulo Correia-de-Sá

Open access · goldAbstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

30 citing papers in PubMed, 58 citations in OpenAlex.

  1. Silencing P2YCell communication and signaling : CCS · 2025
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  4. Review
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  6. The mutual interplay of redox signaling and connexins.Journal of molecular medicine (Berlin, Germany) · 2021
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Light-induced ATP release from the lens.Purinergic signalling · 2018
    Article
  12. Bradykinin-mediated CaJournal of cellular and molecular medicine · 2018
    Article
  13. Mechanisms of ATP Release by Inflammatory Cells.International journal of molecular sciences · 2018
    Review
  14. A cyclic pathway of P2 × 7, bradykinin, and dopamine receptor activation induces a sustained articular hyperalgesia in the knee joint of rats.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018
    Article
  15. P2YPurinergic signalling · 2018
    Article
  16. The American journal of tropical medicine and hygiene · 2018
    Article
  17. Article
  18. Article
  19. Article
  20. 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

8 authors at 2 institutions in 2 countries.

Ana Rita PinheiroLaboratório de Farmacologia e Neurobiologia, Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, Edif, 2 Piso 4, Porto 4050-313, Portugal. farmacol@icbas.up.pt.
Diogo Paramos-de-Carvalho
Mariana Certal
Cristina Costa
Maria Teresa Magalhães-Cardoso
Fátima Ferreirinha
Maria Adelina Costa
Paulo Correia-de-Sá
Universidade do Porto · PTInstituto Politécnico Nacional · MX

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic musculoskeletal pain involves connective tissue remodeling triggered by inflammatory mediators, such as bradykinin. Fibroblast cells signaling involve changes in intracellular Ca2+ ([Ca2+]i). ATP has been related to connective tissue mechanotransduction, remodeling and chronic inflammatory pain, via P2 purinoceptors activation. Here, we investigated the involvement of ATP in bradykinin-induced Ca2+ signals in human subcutaneous fibroblasts.

resultsBradykinin, via B2 receptors, caused an abrupt rise in [Ca2+]i to a peak that declined to a plateau, which concentration remained constant until washout. The plateau phase was absent in Ca2+-free medium; [Ca2+]i signal was substantially reduced after depleting intracellular Ca2+ stores with thapsigargin. Extracellular ATP inactivation with apyrase decreased the [Ca2+]i plateau. Human subcutaneous fibroblasts respond to bradykinin by releasing ATP via connexin and pannexin hemichannels, since blockade of connexins, with 2-octanol or carbenoxolone, and pannexin-1, with 10Panx, attenuated bradykinin-induced [Ca2+]i plateau, whereas inhibitors of vesicular exocytosis, such as brefeldin A and bafilomycin A1, were inactive. The kinetics of extracellular ATP catabolism favors ADP accumulation in human fibroblast cultures. Inhibition of ectonucleotidase activity and, thus, ADP formation from released ATP with POM-1 or by Mg2+ removal from media reduced bradykinin-induced [Ca2+]i plateau. Selective blockade of the ADP-sensitive P2Y12 receptor with AR-C66096 attenuated bradykinin [Ca2+]i plateau, whereas the P2Y1 and P2Y13 receptor antagonists, respectively MRS 2179 and MRS 2211, were inactive. Human fibroblasts exhibited immunoreactivity against connexin-43, pannexin-1 and P2Y12 receptor.

conclusionsBradykinin induces ATP release from human subcutaneous fibroblasts via connexin and pannexin-1-containing hemichannels leading to [Ca2+]i mobilization through the cooperation of B2 and P2Y12 receptors.

Indexed as

Adenosine DiphosphateAdenosine TriphosphateBradykininCalcium SignalingCells, CulturedConnexin 43ConnexinsFibroblastsHumansMiddle AgedNerve Tissue ProteinsReceptor, Bradykinin B2Receptors, Purinergic P2Y12Adenosine DiphosphateAdenosine TriphosphateBradykininConnexin 43ConnexinsNerve Tissue ProteinsP2RY12 protein, humanPANX1 protein, humanReceptor, Bradykinin B2Receptors, Purinergic P2Y12

Identifiers

PMID24047499
PMCPMC3848849
OpenAlexW2138450288

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.