Cyclic nucleotides (cGMP and cAMP) as intracellular second messengers
cyclic GMP (cGMP)
All eukaryotic cells utilize cyclic nucleotides—specifically cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)—as intracellular messengers in a wide variety of cell signaling pathways. Many physiological signals (sensory stimuli, hormones, and neurotransmitters) trigger changes in the cellular levels of these two second messengers which regulate a wide array of physiological processes, such as vision, olfaction, gustation, synaptic transmission, muscle contraction, energy metabolism, immune responses, and regulation of gene expression.
The metabolism of cGMP or cAMP is controlled by regulating its synthesis (carried out by guanylate or adenylate cyclases) and/or its breakdown (by cyclic nucleotide phosphodiesterases). Cytoplasmic levels of cyclic nucleotides may also be modulated nonenzymatically by sequestration by cGMP/cAMP binding proteins or by transport mechanisms that cause cGMP/cAMP efflux from the cell.
Changes in cytoplasmic cyclic nucleotide concentration affect signaling pathways by changing the extent of binding to specific binding proteins (receptors). Targets of action include: cGMP/cAMP dependent protein kinases (PKG and PKA), cyclic nucleotide-gated (CNG) ion channels, cGMP-binding PDEs, and other cyclic nucleotide binding proteins.
The metabolism of cGMP or cAMP is controlled by regulating its synthesis (carried out by guanylate or adenylate cyclases) and/or its breakdown (by cyclic nucleotide phosphodiesterases). Cytoplasmic levels of cyclic nucleotides may also be modulated nonenzymatically by sequestration by cGMP/cAMP binding proteins or by transport mechanisms that cause cGMP/cAMP efflux from the cell.
Changes in cytoplasmic cyclic nucleotide concentration affect signaling pathways by changing the extent of binding to specific binding proteins (receptors). Targets of action include: cGMP/cAMP dependent protein kinases (PKG and PKA), cyclic nucleotide-gated (CNG) ion channels, cGMP-binding PDEs, and other cyclic nucleotide binding proteins.
