Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface.

This award sparked extensive research into cAMP, while cGMP received less attention, with its biological functions largely unknown until the 1980s.

[6]cGMP acts as a regulator of ion channel conductance, glycogenolysis, cellular apoptosis, and platelet inhibition.

The attraction is mediated by the increased levels of soluble guanylate cyclase (sGC) that are present in the apical dendrites.

[10] The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-phosphodiesterase (PDE) pathway has become a target in developing treatments for heart failure.

A deficit in cGMP levels has been associated with adverse cardiovascular outcomes, promoting factors like myocardial fibrosis, vasoconstriction, and inflammation, all of which accelerate heart failure progression.

[11] Some soluble guanylate cyclase (sGC) stimulators, have yielded promising outcomes in reducing cardiovascular events.

[12] The cGMP signaling pathway plays a role in the regulation of neuroplasticity, an area of interest in understanding the pathophysiology of major depressive disorder (MDD).

[13] Enhancing cGMP levels, either by stimulating guanylate cyclase or inhibiting PDEs, promotes neurogenesis and synaptic plasticity, particularly in brain regions implicated in MDD, such as the hippocampus and prefrontal cortex.

[13] Genetic research has further highlighted specific polymorphisms in PDE genes associated with MDD susceptibility and treatment response.

[13] Certain pathogens, such as Enterotoxigenic Escherichia coli (ETEC), elevate cGMP to evade host immune defenses and establish infection.

Once activated, PKG phosphorylates various target proteins, altering their function and contributing to cellular processes such as smooth muscle relaxation, ion channel regulation, and inhibition of platelet aggregation.