Cyclic Nucleotide Metabolism - cGMP. SIGMA-ALDRICH. Cyclic Nucleotide Metabolism - cGMP
Cyclic nucleotides have been extensively studied as second messengers of intracellular events initiated by activation of many types of hormone and neurotransmitter receptors. Cyclic guanosine monophosphate (cGMP) serves as a second messenger in a manner similar to that observed with cAMP. Peptide hormones, such as the natriuretic factors, activate receptors that are associated with membrane-bound guanylate cyclase (GC). Receptor activation of GC leads to the conversion of GTP to cGMP. Nitric oxide (NO) also stimulates cGMP production by activating soluble GC, perhaps by binding to the heme moiety of the enzyme. Similar to cAMP, cGMP mediates most of its intracellular effects through the activation of specific cGMP dependent protein kinases (PKG). Several families of phosphodiesterases (PDE-I-VI) act as regulatory switches by catalyzing the degradation of cGMP to guanosine-5’-monophosphate (5’-GMP). PDE I is stimulated by Ca2+ -calmodulin, perhaps through phosphorylation by PKA. PDE II is a low affinity PDE that can cleave both cAMP and cGMP. The activity of PDE II is stimulated by cGMP. PDE III is inhibited by cGMP while PED V binds to cGMP and plays a role in regulating smooth muscle contraction. PDE VI is a high affinity PDE specifically localized in photoreceptors that is selective for cGMP.
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