Figure 1.

Schematic of the Cyclic GMP (cGMP) signaling pathway. cGMP is synthesized from GTP by soluble guanylate cyclases (sGCα₁β₁ or sGCα₂β₁) in response to nitric oxide (NO) e.g., as generated by the conversion of L-arginine (L-Arg) by NO synthase 3 (NOS3), or by the membrane guanylate cyclase (natriuretic peptide) receptors (NPR) which are activated by peptide hormones [e.g., atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)]. cGMP binds to and activates cGMP-dependent protein kinase G (PKG) and is hydrolyzed by phosphodiesterases (such as PDE5, the target for sildenafil). The insets depict a schematic overview of the structure of NOS3, NPR, PKG, PDE, and sGC.