cAMP (adenosine 3â5â-cyclic monophosphate) is a ubiquitous intracellular second messenger that mediates a diverse range of cellular processes in all organisms from bacteria to higher eukaryotes. It is converted from adenosine triphosphate (ATP) by adenylyl cyclases (ACs), and is inactivated by phosphodiesterases (PDEs) which catalyze its hydrolysis to 5â-AMP. In mammals, upon interaction with extracellular ligands, G protein coupled receptors (GPCRs) linked to GÎ±s activate the family of nine transmembrane ACs to increase intracellular cAMP. In contrast, GPCRs associated with GÎ±i/o inhibit the synthesis of cAMP by transmembrane ACs. cAMP binds and activates protein kinase A (PKA), the guanine nucleotide exchange factors Epac1/2, and cyclic nucleotide-gated ion channels. It can be released extracellularly where it is converted to adenosine by phosphodiesterases and nucleotidases.