Evidence map›Paper›PMID 21135206›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

Exquisite sensitivity to subsecond, picomolar nitric oxide transients conferred on cells by guanylyl cyclase-coupled receptors.

Andrew M Batchelor, Katalin Bartus, Clare Reynell, Sophie Constantinou, Edward J Halvey, Kara F Held, Wolfgang R Dostmann, Jeffrey Vernon, John Garthwaite

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
5.6field-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

46 citing papers in PubMed, 99 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Article
  5. CO and NO Coordinate Developmental Neuron Migration.International journal of molecular sciences · 2025
    Article
  6. Article
  7. NO signal.Nature chemical biology · 2023
    Article
  8. Review
  9. Science translational medicine · 2022
    Article
  10. Article
  11. Review
  12. Article
  13. Differential ligand-selective control of opposing enzymatic activities within a bifunctional c-di-GMP enzyme.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Functional properties of beetroot (Nutrition & metabolism · 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

9 authors at 2 institutions in 2 countries.

Andrew M BatchelorWolfson Institute for Biomedical Research, University College London, Gower Street, London WCIE 6BT, United Kindom.
Katalin Bartus
Clare Reynell
Sophie Constantinou
Edward J Halvey
Kara F Held
Wolfgang R Dostmann
Jeffrey Vernon
John Garthwaite
University College London · GBUniversity of Vermont · US

Funding

Epidemiological and Genetic Studies of Body Mass IndexR01HL068891 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI MYERS, RICHARD H · 2002 to 2007
$4.0M
Exploring Vasomotor Mechanisms using New PKG Inhibitors and cGMP BiosensorsR01HL068991 · NHLBI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI DOSTMANN, WOLFGANG R · 2002 to 2012
$3.4M
Training Program in the Molecular Basis of Cardiovascular DiseaseT32HL007944 · NHLBI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI WARSHAW, DAVID M · 2000 to 2012
$2.9M
NHLBI NIH HHS HL68891NHLBI NIH HHS R01 HL068891NHLBI NIH HHS R01 HL068991NHLBI NIH HHS T323 HL07944NHLBI NIH HHS T32 HL007944Wellcome Trust 081512
6 · The paper itself

Abstract

Nitric oxide (NO) functions as a diffusible transmitter in most tissues of the body and exerts its effects by binding to receptors harboring a guanylyl cyclase transduction domain, resulting in cGMP accumulation in target cells. Despite its widespread importance, very little is known about how this signaling pathway operates at physiological NO concentrations and in real time. To address these deficiencies, we have exploited the properties of a novel cGMP biosensor, named δ-FlincG, expressed in cells containing varying mixtures of NO-activated guanylyl cyclase and cGMP-hydrolyzing phosphodiesterase activity. Responsiveness to NO, signifying a physiologically relevant rise in cGMP to 30 nM or more, was seen at concentrations as low as 1 pM, making cells by far the most sensitive NO detectors yet encountered. Even cells coexpressing phosphodiesterase-5, a cGMP-activated isoform found in many NO target cells, responded to NO in concentrations as low as 10 pM. The dynamics of NO capture and signal transduction was revealed by administering timed puffs of NO from a local pipette. A puff lasting only 100 ms, giving a calculated peak intracellular NO concentration of 23 pM, was detectable. The results could be encapsulated in a quantitative model of cellular NO-cGMP signaling, which recapitulates the NO responsiveness reported previously from crude cGMP measurements on native cells, and which explains how NO is able to exert physiological effects at extremely low concentrations, when only a tiny proportion of its receptors would be occupied.

Indexed as

AnimalsBiosensing TechniquesCattleCyclic GMPCyclic Nucleotide Phosphodiesterases, Type 5Dose-Response Relationship, DrugHEK293 CellsHumansNitric OxideReceptors, Guanylate Cyclase-CoupledSignal TransductionCyclic GMPCyclic Nucleotide Phosphodiesterases, Type 5Nitric OxideReceptors, Guanylate Cyclase-Coupled

Identifiers

PMID21135206
PMCPMC3009818
OpenAlexW1991149890

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.