Evidence map›Paper›PMID 25572823›Full record

ArticleBritish journal of pharmacology2015

GPCR-mediated EGF receptor transactivation regulates TRPV4 action in the vasculature.

Mahmoud Saifeddine, Mahmoud El-Daly, Koichiro Mihara, Nigel W Bunnett, Peter McIntyre, Christophe Altier, Morley D Hollenberg, Rithwik Ramachandran

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

Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% 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, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Aortic smooth muscle TRPV4 channels regulate vasoconstriction in high salt-induced hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2023
    Article
  8. Independent endothelial functions of PIEZO1 and TRPV4 in hepatic portal vein and predominance of PIEZO1 in mechanical and osmotic stress.Liver international : official journal of the International Association for the Study of the Liver · 2023
    Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Renal vascular TRP channels.Current research in physiology · 2021
    Article
  17. Article
  18. Transient receptor potential cation channel subfamily V and breast cancer.Laboratory investigation; a journal of technical methods and pathology · 2020
    Review
  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 3 institutions in 3 countries.

Mahmoud SaifeddineDepartment of Physiology and Pharmacology, Inflammation Research Network and Snyder Institute for Chronic Disease, University of Calgary, Calgary, AB, Canada.
Mahmoud El-Daly
Koichiro Mihara
Nigel W Bunnett
Peter McIntyre
Christophe Altier
Morley D Hollenberg
Rithwik Ramachandran
University of Calgary · CAMonash University · AURMIT University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeTransient receptor potential vanilloid-4 (TRPV4) is a calcium-permeant ion channel that is known to affect vascular function. The ability of TRPV4 to cause a vasoconstriction in blood vessels has not yet been mechanistically examined. Further in neuronal cells, TRPV4 signalling can be potentiated by GPCR activation. Thus, we studied the mechanisms underlying the vascular contractile action of TRPV4 and the GPCR-mediated potentiation of such vasoconstriction, both of which are as yet unappreciated aspects of TRPV4 function. EXPERIMENTAL APPROACH: The mechanisms of TRPV4-dependent regulation of vascular tone in isolated mouse aortae were studied using wire myography. TRPV4-dependent calcium signalling and prostanoid production was studied in cultured human umbilical vein endothelial cells (HUVECs). KEY

resultsIn addition to the well-documented vasorelaxation response triggered by TRPV4 activation, we report here a TRPV4-triggered vasoconstriction in the mouse aorta that involves a COX-generated Tx receptor (TP) agonist that acts in a MAPK and Src kinase signalling dependent manner. This constriction is potentiated by activation of the GPCRs for angiotensin (AT1 receptors) or proteinases (PAR1 and PAR2) via transactivation of the EGF receptor and a process involving PKC. TRPV4-dependent vascular contraction can be blocked by COX inhibitors or with TP antagonists. Further, TRPV4 activation in HUVECs stimulated Tx release as detected by an elisa. CONCLUSION AND IMPLICATIONS: We conclude that the GPCR potentiation of TRPV4 action and TRPV4-dependent Tx receptor activation are important regulators of vascular function and could be therapeutically targeted in vascular diseases.

Indexed as

AnimalsAortaErbB ReceptorsHumansHuman Umbilical Vein Endothelial CellsMiceMice, KnockoutMyographyReceptors, G-Protein-CoupledSignal TransductionTranscriptional ActivationTRPV Cation ChannelsVasoconstrictionErbB ReceptorsReceptors, G-Protein-CoupledTrpv4 protein, mouseTRPV Cation Channels

Identifiers

PMID25572823
PMCPMC4409902
OpenAlexW1911830000

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.