biostudies-literatureManfra OThe Family Blix Foundation, The Simon Fougner Hartmann Family Foundation, grants from the University of OsloBritish Heart FoundationSouth-Eastern Norway Regional Health AuthorityThe Anders Jahre Foundation for the Promotion of ScienceThe Research Council of NorwayNorwegian Council on Cardiovascular Diseases1506-1519https://www.ebi.ac.uk/biostudies/studies/S-EPMC9074987biostudies-literatureUnknown118(6)<h4>Aims</h4>Guanylyl cyclase-B (GC-B; natriuretic peptide receptor-B, NPR-B) stimulation by C-type natriuretic peptide (CNP) increases cGMP and causes a lusitropic and negative inotropic response in adult myocardium. These effects are not mimicked by NPR-A (GC-A) stimulation by brain natriuretic peptide (BNP), despite similar cGMP increase. More refined methods are needed to better understand the mechanisms of the differential cGMP signalling and compartmentation. The aim of this work was to measure cGMP near proteins involved in regulating contractility to understand compartmentation of cGMP signalling in adult cardiomyocytes.<h4>Methods and results</h4>We constructed several fluorescence resonance energy transfer (FRET)-based biosensors for cGMP subcellularly targeted to phospholamban (Cardiovascular researchCNP regulates cardiac contractility and increases cGMP near both SERCA and TnI: difference from BNP visualized by targeted cGMP biosensors.PMC907498720516730349020190512011025RG/17/6/32944Meier SNikolaev VOLevy FOMelleby AOCalamera GAasrum MArunthavarajah DSurdo NCZaccolo MFroese AMoltzau LRAndressen KWManfra OAronsen JMfalseCNP regulates cardiac contractility and increases cGMP near both SERCA and TnI: difference from BNP visualized by targeted cGMP biosensors.<h4>Aims</h4>Guanylyl cyclase-B (GC-B; natriuretic peptide receptor-B, NPR-B) stimulation by C-type natriuretic peptide (CNP) increases cGMP and causes a lusitropic and negative inotropic response in adult myocardium. These effects are not mimicked by NPR-A (GC-A) stimulation by brain natriuretic peptide (BNP), despite similar cGMP increase. More refined methods are needed to better understand the mechanisms of the differential cGMP signalling and compartmentation. The aim of this work was to measure cGMP near proteins involved in regulating contractility to understand compartmentation of cGMP signalling in adult cardiomyocytes.<h4>Methods and results</h4>We constructed several fluorescence resonance energy transfer (FRET)-based biosensors for cGMP subcellularly targeted to phospholamban (2022-01-01T00:00:00Z2022 May2025-05-29T14:36:40.738Z2025-05-29T14:36:40.738ZS-EPMC90749873397022410.1093/cvr/cvab167