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Cyclic guanosine monophosphate
Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP, most notably by activating intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface.
cGMP synthesis is catalyzed by guanylate cyclase (GC) which converts GTP to cGMP. Membrane-bound GC is activated by peptide hormones such as the natriuretic factors , while nitric oxide typically stimulates cGMP synthesis in soluble GC.
cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. It also relaxes smooth muscle tissues. In blood vessels, relaxation of vascular smooth muscles lead to vasodilation and increased blood flow.
Phosphodiesterase inhibitors prevent the degradation of cGMP, thereby enhancing and/or prolonging its effects. For example, Sildenafil (Viagra®) enhances the vasodilatory effects of cGMP within the corpus cavernosum by inhibiting PDE 5 (or PDE V). This is used as a treatment for erectile dysfunction.
Protein kinase activation
cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (protein kinase G ) is a dimer consisting of one catalytic and one regulatory unit, with the regulatory units blocking the active sites of the catalytic units.
cGMP binds to sites on the regulatory units of PKG and activates the catalytic units, enabling them to phosphorylate their substrates. Unlike with the activation of some other protein kinases, notably PKA, the PKG is activated but the catalytic and regulatory units do not disassociate.
- Francis SH, Corbin JD. "Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP action." Crit Rev Clin Lab Sci. 1999 Aug;36(4):275-328. PMID 10486703
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