ArticleCirculation research2010
Feedback control through cGMP-dependent protein kinase contributes to differential regulation and compartmentation of cGMP in rat cardiac myocytes.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 99 citations in OpenAlex.
- Proteomic surveys of the mouse heart unveil cardiovascular responses to nitric oxide/cGMP signaling deficiencies.Communications biology · 2025Article
- Real-time imaging of cGMP signaling shows pronounced differences between glomerular endothelial cells and podocytes.Scientific reports · 2024Article
- Add-on multidrug treatment based on quadruple therapy successfully treated worsening heart failure caused by anthracycline-induced cardiomyopathy in a survivor of cancer as a young adult: a case report.BMC cardiovascular disorders · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Natriuretic peptide pathways in heart failure: further therapeutic possibilities.Cardiovascular research · 2023Article
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.Pflugers Archiv : European journal of physiology · 2021Review
- Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1.Cells · 2020Article
- Muscarinic-dependent phosphorylation of the cardiac ryanodine receptor by protein kinase G is mediated by PI3K-AKT-nNOS signaling.The Journal of biological chemistry · 2020Article
- Mind the gap (junction): cGMP induced by nitric oxide in cardiac myocytes originates from cardiac fibroblasts.British journal of pharmacology · 2019Article
- Phosphodiesterase 5 inhibition improves contractile function and restores transverse tubule loss and catecholamine responsiveness in heart failure.Scientific reports · 2019Article
- cGMP Signaling in the Cardiovascular System-The Role of Compartmentation and Its Live Cell Imaging.International journal of molecular sciences · 2018Review
- Phosphodiesterase type 5 and cancers: progress and challenges.Oncotarget · 2017Review
- Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network.Scientific reports · 2017Article
- C-type natriuretic peptide and natriuretic peptide receptor B signalling inhibits cardiac sympathetic neurotransmission and autonomic function.Cardiovascular research · 2016Article
- Cyclic nucleotide regulation of cardiac sympatho-vagal responsiveness.The Journal of physiology · 2016Review
- Roles of phosphodiesterases in the regulation of the cardiac cyclic nucleotide cross-talk signaling network.Journal of molecular and cellular cardiology · 2016Article
- Dexamethasone-dependent modulation of cyclic GMP synthesis in podocytes.Molecular and cellular biochemistry · 2015Article
- Strategies to increase nitric oxide signalling in cardiovascular disease.Nature reviews. Drug discovery · 2015Review
- Efficacy of B-Type Natriuretic Peptide Is Coupled to Phosphodiesterase 2A in Cardiac Sympathetic Neurons.Hypertension (Dallas, Tex. : 1979) · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleWe have shown recently that particulate (pGC) and soluble guanylyl (sGC) cyclases synthesize cGMP in different compartments in adult rat ventricular myocytes (ARVMs).
objectiveWe hypothesized that cGMP-dependent protein kinase (PKG) exerts a feedback control on cGMP concentration contributing to its intracellular compartmentation. METHODS AND
resultsGlobal cGMP levels, cGMP-phosphodiesterase (PDE) and pGC enzymatic activities were determined in purified ARVMs. Subsarcolemmal cGMP signals were monitored in single cells by recording the cGMP-gated current (I(CNG)) in myocytes expressing the wild-type rat olfactory cyclic nucleotide-gated (CNG) channel. Whereas the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) (100 μmol/L) produced little effect on I(CNG), the response increased 2-fold in the presence of the PKG inhibitors KT5823 (50 nmol/L) or DT-2 (2 μmol/L). The effect of KT5823 was abolished in the presence of the nonselective cyclic nucleotide PDE inhibitor 3-isobutyl-1-methylxantine (IBMX) (100 μmol/L) or the selective cGMP-PDE5 inhibitor sildenafil (100 nmol/L). PKG inhibition also potentiated the effect of SNAP on global cGMP levels and fully blocked the increase in cGMP-PDE5 activity. In contrast, PKG inhibition decreased by ≈50% the I(CNG) response to ANP (10 and 100 nmol/L), even in the presence of IBMX. Conversely, PKG activation increased the I(CNG) response to ANP and amplified the stimulatory effect of ANP on pGC activity.
conclusionsPKG activation in adult cardiomyocytes limits the accumulation of cGMP induced by NO donors via PDE5 stimulation but increases that induced by natriuretic peptides. These findings support the paradigm that cGMP is not uniformly distributed in the cytosol and identifies PKG as a key component in this process.
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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.