cGMP-cAMP interplay in cardiac myocytes: a local affair with far-reaching consequences for heart function.

cAMP and cGMP signalling pathways are common targets in the pharmacological treatment of heart failure, and often drugs that modulate the level of these second messengers are simultaneously administered to patients. cGMP can potentially affect cAMP levels by modulating the activity of PDEs (phosphod...

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Main Authors: Stangherlin, A, Zaccolo, M
Format: Journal article
Language:English
Published: 2012
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author Stangherlin, A
Zaccolo, M
author_facet Stangherlin, A
Zaccolo, M
author_sort Stangherlin, A
collection OXFORD
description cAMP and cGMP signalling pathways are common targets in the pharmacological treatment of heart failure, and often drugs that modulate the level of these second messengers are simultaneously administered to patients. cGMP can potentially affect cAMP levels by modulating the activity of PDEs (phosphodiesterases), the enzymes that degrade cyclic nucleotides. This biochemical cross-talk provides the means for drugs that increase cGMP to concomitantly affect cAMP signals. Recent studies using FRET (fluorescence resonance energy transfer) reporters and real-time imaging show that, in cardiac myocytes, the interplay between cGMP and cAMP has different outcomes depending on the specific location where the cross-modulation occurs. cGMP can either increase or decrease the cAMP response to catecholamines, based on the cyclase that generates it and on the PDEs associated with each subcellular compartment. cGMP-mediated modulation of cAMP signals has functional relevance as it affects protein phosphorylation downstream of protein kinase A and myocyte contractility. The physical separation of positive and negative modulation of cAMP levels by cGMP offers the previously unrecognized possibility to selectively modulate local cAMP signals to improve the efficacy of therapy.
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spelling oxford-uuid:2a1d4a5d-22b0-4207-ba57-27b5ff367d572022-03-26T12:23:07ZcGMP-cAMP interplay in cardiac myocytes: a local affair with far-reaching consequences for heart function.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2a1d4a5d-22b0-4207-ba57-27b5ff367d57EnglishSymplectic Elements at Oxford2012Stangherlin, AZaccolo, McAMP and cGMP signalling pathways are common targets in the pharmacological treatment of heart failure, and often drugs that modulate the level of these second messengers are simultaneously administered to patients. cGMP can potentially affect cAMP levels by modulating the activity of PDEs (phosphodiesterases), the enzymes that degrade cyclic nucleotides. This biochemical cross-talk provides the means for drugs that increase cGMP to concomitantly affect cAMP signals. Recent studies using FRET (fluorescence resonance energy transfer) reporters and real-time imaging show that, in cardiac myocytes, the interplay between cGMP and cAMP has different outcomes depending on the specific location where the cross-modulation occurs. cGMP can either increase or decrease the cAMP response to catecholamines, based on the cyclase that generates it and on the PDEs associated with each subcellular compartment. cGMP-mediated modulation of cAMP signals has functional relevance as it affects protein phosphorylation downstream of protein kinase A and myocyte contractility. The physical separation of positive and negative modulation of cAMP levels by cGMP offers the previously unrecognized possibility to selectively modulate local cAMP signals to improve the efficacy of therapy.
spellingShingle Stangherlin, A
Zaccolo, M
cGMP-cAMP interplay in cardiac myocytes: a local affair with far-reaching consequences for heart function.
title cGMP-cAMP interplay in cardiac myocytes: a local affair with far-reaching consequences for heart function.
title_full cGMP-cAMP interplay in cardiac myocytes: a local affair with far-reaching consequences for heart function.
title_fullStr cGMP-cAMP interplay in cardiac myocytes: a local affair with far-reaching consequences for heart function.
title_full_unstemmed cGMP-cAMP interplay in cardiac myocytes: a local affair with far-reaching consequences for heart function.
title_short cGMP-cAMP interplay in cardiac myocytes: a local affair with far-reaching consequences for heart function.
title_sort cgmp camp interplay in cardiac myocytes a local affair with far reaching consequences for heart function
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AT zaccolom cgmpcampinterplayincardiacmyocytesalocalaffairwithfarreachingconsequencesforheartfunction