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Cyclic guanosine monophosphate (cGMP) is a second messenger derived from GTP.

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.

Contents

Synthesis

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.


Effects

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.


Degradation

Cyclic nucleotide phosphodiesterases (PDE 1-6) degrade cGMP by hydrolyzing cGMP into 5'-GMP.


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.


References

  • 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 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10486703&dopt=Abstract)

  Results from FactBites:
 
cGMP Accumulation Induced by Hypertonic Stress in Dictyostelium discoideum -- Oyama 271 (10): 5574 -- Journal of ... (4121 words)
The hypertonic stress-induced accumulation of cGMP was observed in a streamer F mutant (NP368) that lacks cGMP-specific phosphodiesterase.
We tested the effect of K252a, a protein kinase inhibitor, and EDTA on the hypertonic stress-induced accumulation of cGMP, since K252a is an enhancer (27) and EDTA is a potential inhibitor (28) of the reducing reagent-induced accumulation of cGMP.
The hypertonic stress-induced accumulation of total cGMP reaches a peak at 10-15 min, which is distinct from the receptor-mediated activation of guanylate cyclase that lasts 10 s(13, 14).
  More results at FactBites »

 
 

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