Evidence map›Paper›PMID 20530128›Full record

ArticleMolecular pharmacology2010

Equilibrium between adenylyl cyclase and phosphodiesterase patterns adrenergic agonist dose-dependent spatiotemporal cAMP/protein kinase A activities in cardiomyocytes.

Vania De Arcangelis, Shubai Liu, Dawen Zhang, Dagoberto Soto, Yang K Xiang

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

Article in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
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  15. The novel chromogranin A-derived serpinin and pyroglutaminated serpinin peptides are positive cardiac β-adrenergic-like inotropes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012
    Article
  16. Article
  17. Phosphodiesterases coordinate cAMP propagation induced by two stimulatory G protein-coupled receptors in hearts.Proceedings of the National Academy of Sciences of the United States of America · 2012
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  20. Review
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

5 authors at 1 institution in 1 country.

Vania De ArcangelisDepartment of Molecular and Integrative Physiology, University of Illinois at Urbana Champaign, 407 S. Goodwin Avenue, Urbana, IL 61801, USA.
Shubai Liu
Dawen Zhang
Dagoberto Soto
Yang K Xiang
University of Illinois Urbana-Champaign · US

Funding

Spatiotemporal regulation of beta adrenoceptor signaling in cardiacmyocytesR01HL082846 · NHLBI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI XIANG, YANG K · 2006 to 2014
$3.0M
NHLBI NIH HHS HL082646NHLBI NIH HHS R01 HL082846
6 · The paper itself

Abstract

Beta-adrenergic receptor induces cAMP/Protein kinase A (PKA) activation to regulate cardiac contraction. Using real-time fluorescence resonance energy transfer imaging for highly sensitive detection of cAMP and PKA activities, we show two distinct phases in isoproterenol dose-dependent responses in cardiomyocytes: a transient and dose-dependent increase in cAMP and PKA activities at lower concentrations from 10(-12) to 10(-8) M; and a saturated initial increases at higher concentrations from 10(-8) to 10(-5) M followed by a rapid decrease to different levels that were later sustained in a dose-dependent manner. The dose-dependent temporal responses are patterned by equilibrium between receptor-activated adenylyl cyclase (AC) and phosphodiesterase (PDE). At lower concentrations, cAMP is produced in an agonist dose-dependent manner with AC as a rate-limiting factor. However, the cAMP activities are confined within local domains for phosphorylation of PDE isoforms in the receptor complex but not for phosphorylation of phospholamban and troponin I. At higher concentrations, isoproterenol promotes a dose-dependent selective dissociation of PDE4D but not ACVI from the receptor complex, which shifts the equilibrium between AC and PDE. This shifted balance leads to sustained cAMP accumulation and diffusion for PKA phosphorylation of phospholamban and troponin I, and for myocyte contraction. Pharmacological inhibition or overexpression of either ACVI or PDE4D8 disrupts the balance and shapes the temporal responses in cAMP accumulation. Together, our data reveal a new paradigm for adrenergic agonist dose-dependent cAMP/PKA activities for substrate-specific phosphorylation dictated by dual regulation of AC and PDE in cardiomyocytes.

Indexed as

3',5'-Cyclic-AMP PhosphodiesterasesAdenylyl CyclasesAdrenergic AgonistsAnimalsAnimals, NewbornCalcium-Binding ProteinsCyclic AMP-Dependent Protein KinasesIsoproterenolMiceMice, Inbred StrainsMice, Mutant StrainsMyocardial ContractionMyocytes, CardiacPhospholambanPhosphorylationReceptors, Adrenergic, beta3',5'-Cyclic-AMP PhosphodiesterasesAdenylyl CyclasesAdrenergic AgonistsCalcium-Binding ProteinsCyclic AMP-Dependent Protein KinasesIsoproterenolPhospholambanReceptors, Adrenergic, betaReceptors, Adrenergic, beta-2

Identifiers

PMID20530128
PMCPMC2939479
OpenAlexW2158755243

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.