cAMPcGMP

cAMPcGMP refers to the coordinated signaling roles of two cyclic nucleotide second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These messengers are produced inside cells in response to extracellular signals such as hormones, neurotransmitters, nitric oxide, and light. cAMP is synthesized from ATP by adenylyl cyclase, while cGMP is produced from GTP by guanylyl cyclase. Both are degraded by phosphodiesterases that convert them to noncyclic nucleotides (AMP or GMP), thereby terminating signaling.

The primary intracellular targets of these molecules are protein kinases: cAMP activates protein kinase A (PKA), and cGMP activates protein kinase G (PKG). In addition, cAMP can activate EPAC proteins (exchange proteins activated by cAMP), expanding the range of cAMP-dependent effects. Through these effectors, cAMP and cGMP regulate phosphorylation events that influence metabolism, gene expression, ion channel activity, cytoskeletal organization, and other cellular processes.

Cross-talk between cAMP and cGMP signaling is a notable feature and is mediated largely by phosphodiesterases (PDEs), which control the levels of both messengers. For example, PDE3 hydrolyzes cAMP but is inhibited by cGMP, PDE2 activity on cAMP is enhanced by cGMP, and PDE5 is specific for cGMP. This interplay allows signals such as nitric oxide–driven cGMP production or hormone-induced cAMP changes to influence each other, coordinating responses in tissues like the heart, blood vessels, brain, and sensory organs.

Signaling through cAMP and cGMP is often organized into localized microdomains, enabling specific outputs from distinct pools of these messengers. Dysregulation of their balance is linked to various diseases, and pharmacological targeting of cyclases and PDEs remains a key therapeutic strategy.