Evidence map›Paper›PMID 23086942›Full record

ArticleThe Journal of biological chemistry2012

Intracellular endothelin type B receptor-driven Ca2+ signal elicits nitric oxide production in endothelial cells.

Elena Deliu, G Cristina Brailoiu, Karthik Mallilankaraman, Hong Wang, Muniswamy Madesh, Ashiwel S Undieh, Walter J Koch, Eugen Brailoiu

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-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

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Role of CaCancer medicine · 2026
    Article
  2. Combined Effects of Diosmin, Hesperidin,International journal of molecular sciences · 2025
    Article
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  4. Dopamine internalization via UptakeFrontiers in pharmacology · 2024
    Article
  5. Article
  6. Minimal contribution of IPActa pharmacologica Sinica · 2020
    Article
  7. Article
  8. Article
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  10. Article
  11. Article
  12. Article
  13. Direct evidence of intracrine angiotensin II signaling in neurons.American journal of physiology. Cell physiology · 2014
    Article
  14. Review
  15. 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 1 country.

Elena DeliuDepartment of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
G Cristina Brailoiu
Karthik Mallilankaraman
Hong Wang
Muniswamy Madesh
Ashiwel S Undieh
Walter J Koch
Eugen Brailoiu
Temple University · USThomas Jefferson University · US

Funding

Atherogenic mechanisms with homocysteineR01HL077288 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2004 to 2014
$3.8M
Hyperhomocysteinemia and HDL MetabolismR01HL117654 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2013 to 2017
$3.0M
NADHP Oxidase-mediated MC differentiation & Endothelial Dysfunction in HHcyR01HL110764 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2011 to 2015
$2.5M
Role of nonnuclear estrogen receptor GPR30 in preganglionic vagal neuronsR01HL090804 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI BRAILOIU, EUGEN · 2009 to 2012
$1.5M
NHLBI NIH HHS R01 HL077288NHLBI NIH HHS R01 HL090804NHLBI NIH HHS R01 HL110764NHLBI NIH HHS R01 HL117654NHLBI NIH HHS R01HL90804
6 · The paper itself

Abstract

Endothelin-1 exerts its actions via activation of ET(A) and ET(B) G(q/11) protein-coupled receptors, located in the plasmalemma, cytoplasm, and nucleus. Although the autocrine/paracrine nature of endothelin-1 signaling has been extensively studied, its intracrine role has been largely attributed to interaction with receptors located on nuclear membranes and the nucleoplasm. Because ET(B) receptors have been shown to be targeted to endolysosomes, we used intracellular microinjection and concurrent imaging methods to test their involvement in Ca(2+) signaling and subsequential NO production. We provide evidence that microinjected endothelin-1 produces a dose-dependent elevation in cytosolic calcium concentration in ET(B)-transfected cells and endothelial cells; this response is sensitive to ET(B) but not ET(A) receptor blockade. In endothelial cells, the endothelin-1-induced Ca(2+) response is abolished upon endolysosomal but not Golgi disruption. Moreover, the effect is prevented by inhibition of microautophagy and is sensitive to inhibitors of the phospholipase C and inositol 1,4,5-trisphosphate receptor. Furthermore, intracellular endothelin-1 increases nitric oxide via an ET(B)-dependent mechanism. Our results indicate for the first time that intracellular endothelin-1 activates endolysosomal ET(B) receptors and increase cytosolic Ca(2+) and nitric oxide production. Endothelin-1 acts in an intracrine fashion on endolysosomal ET(B) to induce nitric oxide formation, thus modulating endothelial function.

Indexed as

Calcium SignalingAnimalsAutophagyCalciumCell NucleusCells, CulturedCytosolEndosomesEndothelial CellsEndothelin-1LysosomesMicrocirculationModels, BiologicalNitric OxideOxidation-ReductionRatsCalciumEndothelin-1Nitric OxideReceptor, Endothelin BReceptors, G-Protein-Coupled

Identifiers

PMID23086942
PMCPMC3510805
OpenAlexW2024847675

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.