From the Guidelines
Cyclic adenosine monophosphate (cAMP) is a second messenger molecule that plays a crucial role in cellular signaling, formed from ATP and involved in various physiological processes, including vasorelaxation, as evidenced by its interaction with purinergic subclass A2 receptors to increase cytosolic cAMP levels 1.
Definition and Formation
cAMP is formed from adenosine 5'-triphosphate (ATP) or cyclic adenosine monophosphate, and its production is critical for the transmission of signals from hormones and other extracellular signals to target molecules inside cells. The enzyme adenylyl cyclase, activated by certain hormones or neurotransmitters binding to G-protein coupled receptors, catalyzes this formation.
Physiological Role
The role of cAMP in physiological processes is diverse, including:
- Vasorelaxation: cAMP increases cytosolic levels to cause vasorelaxation, particularly in the microcirculation, with little effect on epicardial conduit arteries, as seen with adenosine's effects 1.
- Metabolism: cAMP regulates metabolic pathways, including glycogen breakdown in the liver.
- Gene expression: cAMP influences gene expression by activating certain transcription factors.
- Ion channel function: cAMP modulates the activity of ion channels, affecting cellular excitability.
- Cell growth: cAMP signaling pathways are involved in the regulation of cell growth and proliferation.
Clinical Significance
Dysregulation of cAMP signaling is implicated in various diseases, making it a target for many medications, including:
- Beta-blockers: which decrease cAMP production by inhibiting adenylyl cyclase.
- Phosphodiesterase inhibitors: which increase cAMP levels by inhibiting its degradation.
- Certain bronchodilators: which utilize cAMP signaling to relax airway smooth muscle.
From the FDA Drug Label
Milrinone, at relevant inotropic and vasorelaxant concentrations, is a selective inhibitor of peak III cAMP phosphodiesterase isozyme in cardiac and vascular muscle This inhibitory action is consistent with cAMP mediated increases in intracellular ionized calcium and contractile force in cardiac muscle, as well as with cAMP dependent contractile protein phosphorylation and relaxation in vascular muscle
- cAMP is involved in mediating increases in intracellular ionized calcium and contractile force in cardiac muscle, as well as contractile protein phosphorylation and relaxation in vascular muscle.
- The exact definition of cAMP is not explicitly stated in the drug label, but it is mentioned as a key component in the mechanism of action of milrinone 2.
From the Research
Definition of cAMP
- Cyclic adenosine 3,5'-monophosphate (cAMP) is a ubiquitous second messenger regulating many biological processes, such as cell migration, differentiation, proliferation, and apoptosis 3, 4, 5.
- cAMP is a nucleotide that acts as a key second messenger in numerous signal transduction pathways, regulating various cellular functions, including cell growth and differentiation, gene transcription, and protein expression 4.
Functions of cAMP
- cAMP signaling functions not only on the plasma membrane but also in the nucleus and in organelles such as mitochondria, maintaining mitochondrial homeostasis, regulating mitochondrial dynamics, and modulating cellular stress responses and other signaling pathways 3.
- cAMP regulates energy homeostasis and nutrient partitioning, mediating the effects of glucagon and epinephrine on hepatic glycogenolysis, and triggering metabolic programs in insulin-responsive tissues 6.
- cAMP activates the phosphorylating enzyme, protein kinase A, which phosphorylates and regulates enzyme substrates involved in intermediary metabolism, and phosphorylates and activates transcription factors critical for gene regulation 5.
Role of cAMP in Disease
- cAMP signaling pathway has been implicated in the development of diseases, including cancer, with cAMP regulating cell growth by different mechanisms, stimulating cell growth in many cell types while inhibiting cell growth in others 4, 7.
- Increasing cAMP levels in cells can reduce the proliferation of tumor cells, with selective PDE3 inhibitors decreasing cell viability in cervical (HeLa) and breast cancer (MCF-7) cell lines 7.