Cyclic guanosine monophosphate signaling pathway (cGMP signaling pathway)

The cGMP signaling pathway involves the synthesis of cyclic guanosine monophosphate (cGMP) from GTP by guanylyl cyclases, triggered by extracellular signals such as nitric oxide or natriuretic peptides. cGMP acts as a second messenger to activate protein kinase G (PKG), cyclic nucleotide-gated ion channels, and phosphodiesterases. This pathway mediates diverse physiological responses—including vasodilation, cardiac remodeling, cell proliferation, apoptosis, visual signal transduction, and platelet function. Therapeutic modulation of the pathway (by PDE5 inhibitors or sGC stimulators) underlies approved treatments for conditions such as erectile dysfunction, pulmonary hypertension, and heart failure, and it is under exploration for repurposing in cancer and other diseases. The pathway is tightly regulated and dysregulation can contribute to pathophysiological states. Importantly, "cGMP signaling pathway" is not a specific molecular entity, but represents a network involving several molecular "targets" (receptors, enzymes).

Other names

cGMP pathwayCyclic GMP signalingNO-cGMP pathwayGuanylate cyclase-cGMP pathway

PDE5 inhibition increases cGMP and causes smooth muscle relaxation/apoptosis in some cells (e.g., sildenafil, tadalafil); sGC stimulation increases cGMP production (e.g., NO donors, Riociguat); cGMP activates PKG, leading to downstream phosphorylation of target proteins involved in cell survival, apoptosis, contractility, and relaxation; cGMP-gated channel modulation (especially in phototransduction and olfaction)