Cyclic Nucleotide Signaling in the Central Nervous System

Publisher Summary Both cAMP and cGMP mediate a wide range of physiological functions, such as regulation of specific cAMP or cGMP phosphodiesterases, protein kinases, ion channels, and several neuronal signal transduction mechanisms. Regulation of CN synthesis and degradation appears to be different in various brain regions, and is modified by several physiological and pathological conditions. cAMP is widely distributed in the CNS. The localization of adenylyl cyclase (AC), the enzyme that produces cAMP, has been studied in the rat brain. The cAMP/PKA signaling pathway has a crucial role in learning in animals as diverse as Aplysia , Drosophila , and mammals, and is involved in activity-dependent forms of synaptic plasticity, such as long-term potentiation (LTP). This pathway culminates in the phosphorylation and activation of critical transcription factors. Cyclic AMP-responsive element-binding protein (CREB) is perhaps the best characterized stimulus-induced transcription factor. It is well established that NO/cGMP/PKG plays a role in long-term depression. The family of cyclic nucleotide-regulated channels comprises two groups: the cyclic nucleotide-gated (CNG) channels, and the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. CNG cation channels are ion channels whose activation is mediated by the direct binding of cGMP or cAMP to the channel protein. In mammals, the mechanism for the generation and entrainment of circadian rhythms resides in the hypothalamic suprachiasmatic nuclei (SCN), and the principal signal that adjusts this biological clock with environmental timing is the light–dark cycle. In conclusion, there are a great number of physiological pathways in which cAMP and cGMP are involved in the central nervous system.