cGMP effects

Cyclic guanosine monophosphate (cGMP) is an important secondary messenger synthesized by guanylate cyclases. cGMP has effects on phosphodiesterases (PDE), ion-gated channels, and the cGMP-dependent protein kinases (cGK, Protein Kinase G or PKG). It is involved in regulation of several physiological functions including vasodilation, platelet aggregation and neurotransmission. Elevation of intracellular cGMP activates PKG which regulates several intracellular molecules and pathways including the vasodilator-stimulated phosphoprotein (VASP) and the ERK pathway. cGMP mediates nitric oxide (NO)-induced vascular smooth muscle relaxation. Phosphodiesterase 5 (PDE5) hydrolyzes cGMP; the PDE5 inhibitor sildenafil (Viagra) increases intracellular cGMP and thereby can be used as a treatment for erectile dysfunction. The role of the cGMP and PKG in platelet activation was controversial as increases in platelet cGMP levels were observed in response to both platelet agonists (thrombin, ADP or collagen) and inhibitors (NO donors such as sodium nitroprusside), but it is currently accepted that PKG inhibits platelet activation. Consistent with this, nitric oxide (NO) donors that inhibit platelet activation enhance intracellular cGMP. cGMP also plays an important stimulatory role in GPIb-IX-mediated platelet activation. Platelet responses to cGMP have been proposed to be biphasic, consisting of an early stimulatory response that promotes platelet activation followed by a delayed platelet inhibition that serves to limit the size of platelet aggregates.

Summary from Reactome (R-HSA-418457), read 2026-09-23.