ArticleProceedings of the National Academy of Sciences of the United States of America1998
Increased expression of adenylylcyclase type VI proportionately increases beta-adrenergic receptor-stimulated production of cAMP in neonatal rat cardiac myocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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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Who cites it
37 citing papers in PubMed, 127 citations in OpenAlex.
- Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure: A Randomized Clinical Trial.JAMA cardiology · 2016Trial
- Past, Present and Future of Regenerative Gene Therapy for Ischemic Heart Failure.Journal of cardiovascular translational research · 2026Review
- Progress in Clinical Gene Therapy for Cardiac Disorders.Molecular diagnosis & therapy · 2023Review
- Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Current Landscape of Heart Failure Gene Therapy.Journal of the American Heart Association · 2019Review
- Function of Adenylyl Cyclase in Heart: the AKAP Connection.Journal of cardiovascular development and disease · 2018Review
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- Targeted transgenesis identifies Gαs as the bottleneck in β2-adrenergic receptor cell signaling and physiological function in airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Compartmentalization of β-adrenergic signals in cardiomyocytes.Trends in cardiovascular medicine · 2013Review
- Adenylyl cyclase 2 selectively couples to E prostanoid type 2 receptors, whereas adenylyl cyclase 3 is not receptor-regulated in airway smooth muscle.The Journal of pharmacology and experimental therapeutics · 2012Article
- Prospects for gene transfer for clinical heart failure.Gene therapy · 2012Review
- A kinase-anchoring proteins and adenylyl cyclase in cardiovascular physiology and pathology.Journal of cardiovascular pharmacology · 2011Review
- Unanticipated signaling events associated with cardiac adenylyl cyclase gene transfer.Journal of molecular and cellular cardiology · 2011Review
- Paradoxical attenuation of β2-AR function in airway smooth muscle by Gi-mediated counterregulation in transgenic mice overexpressing type 5 adenylyl cyclase.American journal of physiology. Lung cellular and molecular physiology · 2011Article
- Equilibrium between adenylyl cyclase and phosphodiesterase patterns adrenergic agonist dose-dependent spatiotemporal cAMP/protein kinase A activities in cardiomyocytes.Molecular pharmacology · 2010Article
- Differential regulation of vascular tone and remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus.Circulation research · 2010Article
- Fibroblast-specific expression of AC6 enhances beta-adrenergic and prostacyclin signaling and blunts bleomycin-induced pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2010Article
- Coordinate down-regulation of adenylyl cyclase isoforms and the stimulatory G protein (G(s)) in intestinal epithelial cell differentiation.The Journal of biological chemistry · 2010Article
- beta(1)-Adrenergic receptor vs adenylyl cyclase 6 expression in cardiac myocytes: differences in transgene localization and intracellular signaling.Cellular signalling · 2010Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cellular content of cAMP generated by activation of adenylylcyclase (AC; EC 4.6.1.1) is a key determinant of functional responsiveness in the heart and other tissues. We have tested two hypotheses regarding the relationship between AC content and beta-adrenergic receptor (betaAR)-mediated signal transduction in cardiac myocytes. First, that AC content limits adrenergic signal transduction, and, second, that increased AC, independent of (betaAR) number and G-protein content, yields a proportional increase in betaAR-mediated transmembrane signaling. We used recombinant adenovirus to increase AC isoform VI (ACVI) expression in neonatal cardiac myocytes. Cells that overexpressed ACVI responded to agonist stimulation with marked increases in cAMP production in proportion to protein expressed. In parallel experiments performed on cells transfected with lacZ (control) or ACVI, [3H]forskolin binding, used to assess AC protein expression, was amplified 6-fold, while betaAR-stimulated cAMP production from these cells was increased 7-fold. No changes in betaAR number, or in the heterotrimeric GTP-binding proteins, Galphas or Galphai2, were observed. Previous studies indicate that increased cardiac expression of betaAR or Galphas does not yield proportional increases in transmembrane adrenergic signaling. In contrast, the current data demonstrate that increased ACVI expression provides a proportional increase in beta-adrenergic signal transduction. Our results show that the amount of AC sets a limit on transmembrane beta-adrenergic signaling. We speculate that similar functional responses are possible in other cell types in which AC plays an important physiological role.
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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.