G‐protein‐coupled receptors (GPCRs) are the largest group of cell surface receptors. They are stimulated by a variety of stimuli and signal to different classes of effectors, including several types of ion channels and second messenger‐generating enzymes. Recent technical advances, most importantly in the optical recording with energy transfer techniques––fluorescence and bioluminescence resonance energy transfer, FRET and BRET––, have permitted a detailed kinetic analysis of the individual steps of the signalling chain, ranging from ligand binding to the production of second messengers in intact cells. The transfer of information, which is initiated by ligand binding, triggers a signalling cascade that displays various rate‐controlling steps at different levels. This review summarizes recent findings illustrating the speed and the complexity of this signalling system.

British Journal of Pharmacology (2008) 153, S125–S132; doi:10.1038/sj.bjp.0707656; published online 14 January 2008