Cyclic AMP, also known as cyclic adenosine monophosphate (3′,5′-cyclic AMP or cAMP for short), is a cyclic nucleotide used as a second messenger for intracellular signal transduction in prokaryotes and eukaryotes. It is synthesized by adenylate cyclase and mainly activates protein kinase A (PKA), which regulates various cellular processes through protein phosphorylation. In addition, cAMP directly activates certain channels and enzymes and participates in gene repression and feedback mechanisms. cAMP is also involved in the regulation of glycogen, sugar and lipid metabolism.

Role of cyclic AMP in brain development

Studies have found that cAMP directly promotes axon regeneration of spiral ganglion neurons through PKA and exchange proteins directly activated by cyclic adenosine monophosphate (Epac) and by increasing the level of endogenous neurotrophic factors produced by neurons. In vitro, cAMP analogs have a biphasic effect on neurite length, increasing neurite length at lower concentrations and reducing length at higher concentrations. cAMP also induces axon regeneration by inducing proliferation of mouse Schwann cells and their synthesis and release of neurotrophic factors that promote axon regeneration, and by promoting Schwann cells to express myelination-related genes (MG), and promote myelination regeneration. In addition, molecules of cAMP accumulate in the brains of people with certain mental disorders during periods of stress, and it disconnects neural networks in the prefrontal cortex by forcing certain ion channels to open, like a circuit breaker is triggered to stop the flow of electricity. To keep the network functioning, these channels, called hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, must remain closed. They get some help from another molecule next to the HCN channel, the alpha 2A adrenergic receptor, which, when activated, strengthens the neural networks and keeps them connected by preventing the production of cAMP.

Role of Cyclic AMP in Platelets

Dibutyryl cyclic AMP inhibits platelet aggregation induced by ADP, epinephrine, collagen, and thrombin. Cyclic AMP also has an inhibitory effect, but it is less effective. Collagen, 5-HT, and thrombin can also inhibit adenylate cyclase activity. ADP, dibutyryl cyclic adenosine monophosphate, and cyclic adenosine monophosphate do not change adenylate cyclase activity. A decrease in platelet cyclic adenosine monophosphate favors platelet aggregation, while an increase in cyclic adenosine monophosphate inhibits platelet aggregation.

Role of Cyclic AMP in Oocytes

cAMP is a key second messenger that regulates oocyte maturation. Previous studies have found that spontaneous in vitro maturation of mouse oocytes can be reversibly blocked by the addition of cAMP derivatives after they are released from follicles. Further studies have shown that adenylate cyclase activators, membrane-permeable cAMP analogs, or cAMP phosphodiesterase inhibitors such as hypoxanthine or 3-isobutyl-1-methylxanthine (IBMX) can block oocyte maturation. In addition, oocytes spontaneously resume meiosis as cAMP levels decrease. These findings have been confirmed in many mammalian species and indicate that the maintenance of meiotic arrest in meiotically competent oocytes is dependent on high levels of intracellular cAMP. Intracellular cAMP regulates the activity of maturation-promoting factor (MPF) by stimulating cAMP-dependent protein kinase A (PKA). High cAMP levels lead to phosphorylation of CDK1 and inactivation of the MPF complex, thereby arresting oocytes at the profollicular development stage of prophase I.