ArticleCirculation research2019
Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist.
Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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.
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.
Who cites it
8 citing papers in PubMed.
- The nuclear receptor ROR-alpha is a putative novel myogenic regulator of the cardiomyocyte transcriptome, including the alpha-1A adrenergic receptor.American journal of physiology. Heart and circulatory physiology · 2026Article
- Unheralded Adrenergic Receptor Signaling in Cellular Oxidative Stress and Death.Current opinion in physiology · 2024Article
- Identification of a Novel Subtype-Selective αACS chemical neuroscience · 2024Article
- Gq Signaling in Autophagy Control: Between Chemical and Mechanical Cues.Antioxidants (Basel, Switzerland) · 2022Review
- Electroacupuncture Ameliorates Acute Myocardial Ischemic Injury and Long QT Interval in Mice through theOxidative medicine and cellular longevity · 2022Article
- Sympatho-adrenergic mechanisms in heart failure: new insights into pathophysiology.Medical review (2021) · 2021Article
- Review
- Cardiac α1A-adrenergic receptors: emerging protective roles in cardiovascular diseases.American journal of physiology. Heart and circulatory physiology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
rationaleGq signaling in cardiac myocytes is classically considered toxic. Targeting Gq directly to test this is problematic, because cardiac myocytes have many Gq-coupled receptors.
objectiveTest whether Gq coupling is required for the cardioprotective effects of an alpha-1A-AR (adrenergic receptor) agonist. METHODS AND
resultsIn recombinant cells, a mouse alpha-1A-AR with a 6-residue substitution in the third intracellular loop does not couple to Gq signaling. Here we studied a knockin mouse with this alpha-1A-AR mutation. Heart alpha-1A receptor levels and antagonist affinity in the knockin were identical to wild-type. In wild-type cardiac myocytes, the selective alpha-1A agonist A61603-stimulated phosphoinositide-phospholipase C and myocyte contraction. In myocytes with the alpha-1A knockin, both A61603 effects were absent, indicating that Gq coupling was absent. Surprisingly, A61603 activation of cardioprotective ERK (extracellular signal-regulated kinase) was markedly impaired in the KI mutant myocytes, and A61603 did not protect mutant myocytes from doxorubicin toxicity in vitro. Similarly, mice with the α1A KI mutation had increased mortality after transverse aortic constriction, and A61603 did not rescue cardiac function in mice with the Gq coupling-defective alpha-1A receptor.
conclusionsGq coupling is required for cardioprotection by an alpha-1A-AR agonist. Gq signaling can be adaptive.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.