Adenosine 3,5 -cyclic monophosphate (cAMP) and guanosine 3,5 -cyclic monophosphate are ubiquitous nucleotides that have been described as the first and second messengers. In concert with intracellular calcium and IP3, they play a major role in the control of intracellular signaling, which orchestrates normal and pathophysiological responses. Downstream from the cyclic nucleotide synthesis by adenylyl and guanylyl cyclases, the multigenic family of cyclic nucleotide phosphodiesterases (PDEs), by specifically hydrolyzing cyclic nucleotides, controls cAMP and cGMP levels to maintain a basal...