cGMP-specific 3',5'-cyclic phosphodiesterase 5 (PDE5) (PDE5)

cGMP-specific 3',5'-cyclic phosphodiesterase 5 (PDE5) is a critical regulatory enzyme that modulates vascular tone by catalyzing the hydrolysis of the secondary messenger cyclic guanosine monophosphate (cGMP) [UniProt: O76074]. It is predominantly expressed in the smooth muscle cells of the corpus cavernosum, pulmonary vasculature, and platelets, where it serves as the primary terminator of the nitric oxide-mediated signaling pathway [PMID: 15309021]. By degrading cGMP into 5'-GMP, PDE5 facilitates vasoconstriction and limits the duration of smooth muscle relaxation. In clinical practice, PDE5 is a major therapeutic target for conditions such as erectile dysfunction and pulmonary arterial hypertension, where its inhibition leads to increased cGMP levels and improved blood flow [StatPearls: NBK554397]. Selective inhibitors like sildenafil and tadalafil compete with cGMP for the enzyme's catalytic site, thereby promoting vasodilation through sustained protein kinase G activation [PubChem: SID 46506847]. While highly effective, the therapeutic application of PDE5 inhibitors requires careful management due to potential cross-reactivity with other phosphodiesterase isoforms and dangerous interactions with nitric oxide donors [PMID: 11211782].

Other names

PDE5APhosphodiesterase type 5cGMP-specific phosphodiesterase 5PDE5A1Phosphodiesterase 5A

Selective and competitive inhibition of the PDE5 enzyme prevents the hydrolysis of cyclic guanosine monophosphate (cGMP) into 5'-GMP. This inhibition maintains high intracellular levels of cGMP, which activates protein kinase G (PKG), leading to the phosphorylation of various proteins that facilitate calcium efflux and smooth muscle relaxation.