Nitric oxide synthase–guanylyl cyclase signaling pathway (NOS–GC pathway (may split for individual targets: NOS, GC))

The nitric oxide synthase–guanylyl cyclase signaling pathway mediates the production and cellular signaling of nitric oxide (NO) and cyclic GMP (cGMP). Nitric oxide synthase enzymes convert l-arginine to NO, which diffuses and activates soluble guanylyl cyclase. Activated GC catalyzes GTP conversion to cGMP, a second messenger for smooth muscle relaxation, vascular tone regulation, neurotransmission, platelet aggregation, and immune functions. Dysregulation of this pathway is involved in cardiovascular diseases, neurodegeneration, depression, and immune dysfunction, and both NOS and GC are recognized therapeutic drug targets.

Other names

Nitric oxide signaling pathwayNO–cGMP pathwayNitric oxide–cyclic GMP pathwayNitric oxide synthase/guanylyl cyclase pathway

Stimulation of NOS increases NO production, activating GC, increasing cGMP, causing smooth muscle relaxation and vasodilation. GC inhibitors block cGMP signaling and its physiological effects. PDE5 inhibitors inhibit cGMP degradation, potentiating pathway effects.