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How cAMP generates hormone-specific effects has been debated for many decades. Fluorescence resonance energy transfer (FRET)-based sensors for cAMP allow real-time imaging of the second messenger in intact cells with high spatiotemporal resolution. This technology has made it possible to directly demonstrate that cAMP signals are compartmentalised. The details of such signal compartmentalisation are still being uncovered, and recent findings reveal a previously unsuspected submicroscopic heterogeneity of intracellular cAMP. A model is emerging where specificity depends on compartmentalisation and where the physiologically relevant signals are those that occur within confined nanodomains, rather than bulk changes in cytosolic cAMP. These findings subvert the classical notion of cAMP signalling and provide a new framework for the development of targeted therapeutic approaches.

Original publication




Journal article


Trends Pharmacol Sci

Publication Date





209 - 222


FRET imaging, G protein coupled receptors, cAMP, compartmentalisation, phosphodiesterases, protein kinase A, Animals, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Fluorescence Resonance Energy Transfer, Humans, Receptors, G-Protein-Coupled, Second Messenger Systems, Single Molecule Imaging