ArticleCirculation research2006
A specific pattern of phosphodiesterases controls the cAMP signals generated by different Gs-coupled receptors in adult rat ventricular myocytes.
Article in Circulation research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 174 citations in OpenAlex.
- Combined excitation scan-based hyperspectral imaging and digital deconvolution for the assessment of the kinetic and spatial distributions of cAMP signals.Proceedings of SPIE--the International Society for Optical Engineering · 2026Article
- Review
- Overview of mechanism of electroacupuncture pretreatment for prevention and treatment of cardiovascular and cerebrovascular diseases.CNS neuroscience & therapeutics · 2024Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Hyperspectral imaging and dynamic region of interest tracking approaches to quantify localized cAMP signals.Biochemical Society transactions · 2024Review
- Glucagon and Its Receptors in the Mammalian Heart.International journal of molecular sciences · 2023Review
- Phosphodiesterase 8 governs cAMP/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism.European heart journal · 2023Article
- Acute PDE4 Inhibition Induces a Transient Increase in Blood Glucose in Mice.International journal of molecular sciences · 2023Article
- Ion Channel-Based Reporters for cAMP Detection.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Compartmentalized cAMP signaling in cardiac ventricular myocytes.Cellular signalling · 2022Review
- Mitochondrial A-kinase anchoring proteins in cardiac ventricular myocytes.Physiological reports · 2021Article
- Impact of phosphodiesterases PDE3 and PDE4 on 5-hydroxytryptamine receptor4-mediated increase of cAMP in human atrial fibrillation.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Milestones in the development and implementation of FRET-based sensors of intracellular signals: A biological perspective of the history of FRET.Cellular signalling · 2020Review
- Investigating the effect of sildenafil on improving lung function and quality of life in the patients with severe asthma.Journal of family medicine and primary care · 2019Article
- Article
- PDE4 and mAKAPβ are nodal organizers of β2-ARs nuclear PKA signalling in cardiac myocytes.Cardiovascular research · 2018Article
- Investigating β-adrenergic-induced cardiac hypertrophy through computational approach: classical and non-classical pathways.The journal of physiological sciences : JPS · 2018Article
- cAMP Signaling Compartmentation: Adenylyl Cyclases as Anchors of Dynamic Signaling Complexes.Molecular pharmacology · 2018Review
- Imaging of PDE2- and PDE3-Mediated cGMP-to-cAMP Cross-Talk in Cardiomyocytes.Journal of cardiovascular development and disease · 2018Review
- Compartmentalized cAMP Signaling Associated With Lipid Raft and Non-raft Membrane Domains in Adult Ventricular Myocytes.Frontiers in pharmacology · 2018Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Compartmentation of cAMP is thought to generate the specificity of Gs-coupled receptor action in cardiac myocytes, with phosphodiesterases (PDEs) playing a major role in this process by preventing cAMP diffusion. We tested this hypothesis in adult rat ventricular myocytes by characterizing PDEs involved in the regulation of cAMP signals and L-type Ca2+ current (I(Ca,L)) on stimulation with beta1-adrenergic receptors (beta1-ARs), beta2-ARs, glucagon receptors (Glu-Rs) and prostaglandin E1 receptors (PGE1-Rs). All receptors but PGE1-R increased total cAMP, and inhibition of PDEs with 3-isobutyl-1-methylxanthine strongly potentiated these responses. When monitored in single cells by high-affinity cyclic nucleotide-gated (CNG) channels, stimulation of beta1-AR and Glu-R increased cAMP, whereas beta2-AR and PGE1-R had no detectable effect. Selective inhibition of PDE3 by cilostamide and PDE4 by Ro 20-1724 potentiated beta1-AR cAMP signals, whereas Glu-R cAMP was augmented only by PD4 inhibition. PGE1-R and beta2-AR generated substantial cAMP increases only when PDE3 and PDE4 were blocked. For all receptors except PGE1-R, the measurements of I(Ca,L) closely matched the ones obtained with CNG channels. Indeed, PDE3 and PDE4 controlled beta1-AR and beta2-AR regulation of I(Ca,L), whereas only PDE4 controlled Glu-R regulation of I(Ca,L) thus demonstrating that receptor-PDE coupling has functional implications downstream of cAMP. PGE1 had no effect on I(Ca,L) even after blockade of PDE3 or PDE4, suggesting that other mechanisms prevent cAMP produced by PGE1 to diffuse to L-type Ca2+ channels. These results identify specific functional coupling of individual PDE families to Gs-coupled receptors as a major mechanism enabling cardiac cells to generate heterogeneous cAMP signals in response to different hormones.
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