Nucleotide Messenger

Nucleotide second messengers are key second messenger signalling molecules that carry signals from the extracellular environment to the intracellular compartment. These small molecules, derived from nucleotides such as adenosine triphosphate (ATP) and guanosine triphosphate (GTP), play diverse roles in cellular processes such as cell growth, metabolism, and gene expression. One of the most well-known of the nucleotide second messengers is cyclic adenosine monophosphate (cAMP), which is synthesized from ATP by the enzyme adenylyl cyclase. cAMP acts as a signalling molecule by activating protein kinase A (PKA), which then phosphorylates various target proteins to regulate cellular responses. For example, in response to the binding of hormones such as adrenalin to G protein-coupled receptors (GPCRs), adenylyl cyclase is activated, leading to an increase in cAMP levels. Elevated cAMP then activates PKA, which phosphorylates downstream targets involved in glycogen metabolism, gene expression, and ion channel activity. An additional example of cAMP signalling is the regulation of glycogen breakdown in liver cells in response to glucagon. Glucagon binding to glucagon receptor (also a GPCR) leads to the activation of an associated G protein called Gs (stimulatory G protein). This G protein undergoes a conformational change, allowing it to interact with and activate adenylyl cyclase, stimulating cAMP production, activating PKA. PKA then phosphorylates and activates glycogen phosphorylase, the key enzyme responsible for glycogen breakdown. This enzyme converts glycogen into glucose-1-phosphate by cleaving off glucose units from the glycogen molecule, ultimately leading to the release of glucose from glycogen stores. Another important nucleotide second messenger is cyclic guanosine monophosphate (cGMP). cGMP is synthesized from GTP by the enzyme guanylyl cyclase and plays critical roles in cellular signalling. One notable example of cGMP signalling is in the regulation of smooth muscle relaxation. Nitric oxide (NO), produced by endothelial cells, diffuses to adjacent smooth muscle cells, and activates guanylyl cyclase, leading to an increase in cGMP levels. Elevated cGMP then activates protein kinase G (PKG), which phosphorylates various proteins involved in muscle relaxation, including ion channels and contractile proteins. One key target is myosin light chain phosphatase (MLCP), an enzyme responsible for dephosphorylating the myosin light chain (MLC). By phosphorylating and activating MLCP, PKG enhances its activity. MLCP then removes the phosphate groups from the MLC, resulting in its dephosphorylation. Dephosphorylated MLC leads to decreased myosin-actin cross-bridge formation in the muscle fibres, preventing the contraction of smooth muscle cells, resulting in muscle relaxation. This signalling pathway is crucial for maintaining blood vessel tone and regulating blood pressure. Finally, cyclic adenosine diphosphate ribose (cADPR) is a molecule that functions as a calcium ion (Ca²⁺) mobilizing second messenger. cADPR is synthesized from nicotinamide adenine dinucleotide (NAD+) by the enzyme ADP-ribosyl cyclase. Once produced, cADPR binds to ryanodine receptors (RyRs) located on the endoplasmic reticulum (ER) or sarcoplasmic reticulum (SR) membranes. Binding of cADPR to RyRs causes the release of calcium ions (Ca²⁺) from intracellular stores. This release is known as calcium-induced calcium release (CICR). The released calcium ions contribute to the overall increase in cytosolic calcium levels. We offer a wide product range of research tools for studying nucleotide second messengers, including PDE2A antibodies, PDE4D antibodies, PDE8A antibodies, PDE4C antibodies, and CREB + CREM ELISA Kits. Explore our full nucleotide second messengers product range below and discover more, for less. Alternatively, you can explore our cAMP, GTP, and cGMP product ranges.