Cyclic guanosine monophosphate (cGMP)

Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). 

cGMP acts as a second messenger much like cyclic AMP. 


A key intracellular second messenger mediate protective cardiovascular, renal, neurohormonal, and metabolic actions in the maintenance of whole body homeostasis.



cGMP activates  of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface.



Guanylate cyclase (GC) catalyzes cGMP synthesis. 



Peptide hormones such as the atrial natriuretic factor activate membrane-bound GC.



Soluble GC (sGC) is typically activated by nitric oxide to stimulate cGMP synthesis. 



cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. 



cGMP relaxes smooth muscle tissues In blood vessels, leading  to vasodilation and increased blood flow.



cGMP is also a secondary messenger in phototransduction in the eye. 



cGMP gets synthesized when olfactory receptors receive odorous input. 



cGMP is implicated it in long-term cellular responses to odor stimulation.



cGMP synthesis in the olfactory system  is due to sGC activation by nitric oxide, a neurotransmitter. 



Numerous cyclic nucleotide phosphodiesterases (PDE) can degrade cGMP.



Phosphodiesterase inhibitors prevent the degradation of cGMP, thereby enhancing and/or prolonging its effects. 



Sildenafil (Viagra) and similar drugs enhance the vasodilatory effects of cGMP within the corpus cavernosum by inhibiting PDE 5.



Sildenafil is used as a treatment for erectile dysfunction, bit it can inhibit PDE6 in retina resulting  in loss of visual sensitivity but is unlikely to impair common visual tasks, except under conditions of reduced visibility when objects are already near visual threshold.



The inhibitory visual effects  can bev avoided by other PDE5 inhibitors, such as tadalafil.


The family of peptides call the natriuretic peptides which include atrial natriuretic peptide, B-type natriuretic peptide, and C-type natriuretic peptide are all cyclic GMP activators.



Sacubitril-valsartan augments natriuretic peptides through inhibition of Nepro lysing and suggest a potential of cyclic GMP augmenting therapy for heart failure.







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