ArticleProceedings of the National Academy of Sciences of the United States of America2003
Cardioprotection specific for the G protein Gi2 in chronic adrenergic signaling through beta 2-adrenoceptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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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.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
- Opposite effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Review
- Protective effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Gαi2 regulates the adult myogenesis of masticatory muscle satellite cells.Journal of cellular and molecular medicine · 2023Article
- G protein-coupled receptor signaling: transducers and effectors.American journal of physiology. Cell physiology · 2022Review
- Takotsubo Syndrome: Translational Implications and Pathomechanisms.International journal of molecular sciences · 2022Review
- Analyses of Gnai3-iresGFP reporter mice reveal unknown GαScientific reports · 2021Article
- Participation of GαFrontiers in pharmacology · 2019Article
- G protein, phosphorylated-GATA4 and VEGF expression in the hearts of transgenic mice overexpressing β1- and β2-adrenergic receptors.Molecular medicine reports · 2017Article
- Cardiac physiologic regulation of sub-type specific adrenergic receptors in transgenic mice overexpressing βClinical and experimental emergency medicine · 2016Article
- Sarco"MiR" friend or foe: a perspective on the mechanisms of doxorubicin-induced cardiomyopathy.Annals of translational medicine · 2016Article
- Lack of Gαi2 leads to dilative cardiomyopathy and increased mortality in β1-adrenoceptor overexpressing mice.Cardiovascular research · 2015Article
- Conditional disruption of interactions between Gαi2 and regulator of G protein signaling (RGS) proteins protects the heart from ischemic injury.BMC pharmacology & toxicology · 2014Article
- Article
- Cardiac progenitor cells engineered with βARKct have enhanced β-adrenergic tolerance.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Deletion of the β2-adrenergic receptor prevents the development of cardiomyopathy in mice.Journal of molecular and cellular cardiology · 2013Article
- β-Adrenergic regulation of cardiac progenitor cell death versus survival and proliferation.Circulation research · 2013Article
- High levels of circulating epinephrine trigger apical cardiodepression in a β2-adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy.Circulation · 2012Article
- Gαi2 signaling: friend or foe in cardiac injury and heart failure?Naunyn-Schmiedeberg's archives of pharmacology · 2012Article
- The Role of Inhibitory G Proteins and Regulators of G Protein Signaling in the in vivo Control of Heart Rate and Predisposition to Cardiac Arrhythmias.Frontiers in physiology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Two subtypes of beta-adrenoceptors, beta 1 and beta 2, mediate cardiac catecholamine effects. These two types differ qualitatively, e.g., regarding G protein coupling and calcium channel stimulation. Transgenic mice overexpressing human beta 2-adrenoceptors survive high-expression levels, unlike mice overexpressing beta 1-adrenoceptors. We examined the role of inhibitory Gi proteins, known to be activated by beta 2- but not beta 1-adrenoceptors, on the chronic effects of human beta 2-adrenoreceptor overexpression in transgenic mice. These mice were crossbred with mice where G alpha i2, a functionally important cardiac Gi alpha-subunit, was inactivated by targeted gene deletion. Survival of beta 2-adrenoreceptor transgenic mice was reduced by heterozygous inactivation of G alpha i2. Homozygous knockout/beta 2-adrenoreceptor transgenic mice died within 4 days after birth. Heterozygous knockout/beta 2-adrenoreceptor transgenic mice developed more pronounced cardiac hypertrophy and earlier heart failure compared with beta 2-adrenoreceptor transgenic mice. Single calcium-channel activity was strongly suppressed in heterozygous knockout/beta 2-adrenoreceptor transgenic mice. In cardiomyocytes from these mice, pertussis toxin treatment in vitro fully restored channel activity and enhanced channel activity in cells from homozygous G alpha i2 knockout animals. Cardiac G alpha i3 protein was increased in all G alpha i2 knockout mouse strains. Our results demonstrate that G alpha i2 takes an essential protective part in chronic signaling of overexpressed beta 2-adrenoceptors, leading to prolonged survival and delayed cardiac pathology. However, reduction of calcium-channel activity by beta 2-adrenoreceptor overexpression is due to a different pertussis-toxin-sensitive pathway, most likely by G alpha i3. This result indicates that subtype-specific signaling of beta 2-adrenoreceptor functionally bifurcates at the level of Gi, leading to different effects depending on the G alpha isoform.
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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.