Phosphodiesterases and compartmentalized cAMP signalling in the heart
- PMID: 16466668
- DOI: 10.1016/j.ejcb.2006.01.002
Phosphodiesterases and compartmentalized cAMP signalling in the heart
Abstract
A key feature of the cAMP/cAMP-dependent protein kinase (PKA) transduction system is the compartmentalisation of its signalling enzymes and effectors. Given the large diversity of PKA targets within cardiac cells a precisely regulated and confined activity of such signalling pathway is essential for specificity of response. This appears to be achieved through the generation of local pools of high cAMP and activation of PKA at discrete subcellular locations. Phosphodiesterases (PDEs) are the only route for degrading cAMP and are thus poised to regulate intracellular cAMP gradients. Their spatial confinement to discrete compartments and functional coupling to individual receptors provides an efficient way to control local [cAMP](i) in a stimulus-specific manner. A better understanding of the distinctive role that individual PDEs play in shaping the cAMP signal in heart cells may lead to the development of new strategies for selective pharmacologic manipulation of cAMP signalling in defined functional domains.
Similar articles
-
Compartmentalized phosphodiesterase-2 activity blunts beta-adrenergic cardiac inotropy via an NO/cGMP-dependent pathway.Circ Res. 2006 Feb 3;98(2):226-34. doi: 10.1161/01.RES.0000200178.34179.93. Epub 2005 Dec 15. Circ Res. 2006. PMID: 16357307
-
Sustained exposure to catecholamines affects cAMP/PKA compartmentalised signalling in adult rat ventricular myocytes.Cell Signal. 2016 Jul;28(7):725-32. doi: 10.1016/j.cellsig.2015.10.003. Epub 2015 Oct 22. Cell Signal. 2016. PMID: 26475678 Free PMC article.
-
beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi.Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):940-5. doi: 10.1073/pnas.262787199. Epub 2003 Jan 27. Proc Natl Acad Sci U S A. 2003. Retraction in: Proc Natl Acad Sci U S A. 2022 Apr 26;119(17):e2205198119. doi: 10.1073/pnas.2205198119 PMID: 12552097 Free PMC article. Retracted.
-
Compartmentalized signalling: spatial regulation of cAMP by the action of compartmentalized phosphodiesterases.FEBS J. 2009 Apr;276(7):1790-9. doi: 10.1111/j.1742-4658.2009.06926.x. Epub 2009 Feb 23. FEBS J. 2009. PMID: 19243430 Review.
-
[Cyclic nucleotide phosphodiesterases: therapeutic targets in cardiac hypertrophy and failure].Med Sci (Paris). 2024 Jun-Jul;40(6-7):534-543. doi: 10.1051/medsci/2024083. Epub 2024 Jul 8. Med Sci (Paris). 2024. PMID: 38986098 Review. French.
Cited by
-
Age-Dependent Maturation of iPSC-CMs Leads to the Enhanced Compartmentation of β2AR-cAMP Signalling.Cells. 2020 Oct 12;9(10):2275. doi: 10.3390/cells9102275. Cells. 2020. PMID: 33053822 Free PMC article.
-
Mechanisms of the cyclic nucleotide cross-talk signaling network in cardiac L-type calcium channel regulation.J Mol Cell Cardiol. 2017 May;106:29-44. doi: 10.1016/j.yjmcc.2017.01.013. Epub 2017 Mar 29. J Mol Cell Cardiol. 2017. PMID: 28365422 Free PMC article.
-
Compartmentalization of β-adrenergic signals in cardiomyocytes.Trends Cardiovasc Med. 2013 Oct;23(7):250-6. doi: 10.1016/j.tcm.2013.02.001. Epub 2013 Mar 23. Trends Cardiovasc Med. 2013. PMID: 23528751 Free PMC article. Review.
-
The role of type 4 phosphodiesterases in generating microdomains of cAMP: large scale stochastic simulations.PLoS One. 2010 Jul 22;5(7):e11725. doi: 10.1371/journal.pone.0011725. PLoS One. 2010. PMID: 20661441 Free PMC article.
-
Mouse Cardiac Pde1C Is a Direct Transcriptional Target of Pparα.Int J Mol Sci. 2018 Nov 22;19(12):3704. doi: 10.3390/ijms19123704. Int J Mol Sci. 2018. PMID: 30469494 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
