Molecular diversity of cyclic AMP signalling

Several neuroendocrine control systems are prominently controlled by G-protein coupled receptors that activate the cAMP signal transduction pathway. The discovery of multiple genes that encode the molecular machinery of cAMP metabolism has revolutionized our knowledge of cAMP mediated processes. This perhaps all too familiar second messenger can be generated by nine different membrane enzymes in the context of varied levels of activation of G proteins as well as Ca(2+)- and protein kinase C-dependent processes. The amplitude, length and subcellular distribution of the cAMP signal are further modulated by over twenty functionally distinct isotypes of cAMP-degrading phosphodiesterases in a cell- and stimulus-specific manner. The present review summarizes the key properties of the molecular machinery that generates the cAMP signal and highlights how it is deployed in neuroendocrine systems.