Phosphodiesterase type 5 (PDE5) (PDE5)

Phosphodiesterase type 5 (PDE5) is a zinc-binding enzyme that specifically catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a secondary messenger crucial for smooth muscle relaxation and vasodilation (UniProt, O76074). It is highly expressed in the corpus cavernosum, vascular smooth muscle, and platelets (StatPearls, NBK549843). By degrading cGMP, PDE5 terminates the signaling cascade initiated by nitric oxide, thereby regulating vascular tone (PubMed, PMC3121214). Pharmacological inhibition of PDE5 increases cGMP levels, promoting prolonged vasodilation, which is the primary mechanism for treating erectile dysfunction and pulmonary arterial hypertension (NIH, PubChem CID 5212). PDE5 inhibitors like sildenafil and tadalafil are widely used clinically and are also being investigated for their potential benefits in heart failure and cognitive disorders (PubMed, PMC4007858). Safety considerations include significant drug-drug interactions with nitrates, which can lead to life-threatening hypotension (StatPearls, NBK549843).

Other names

PDE5AcGMP-specific 3',5'-cyclic phosphodiesterasePhosphodiesterase 5AcGMP-specific phosphodiesterase type 5

PDE5 inhibitors competitively bind to the catalytic site of the enzyme, preventing the hydrolysis of cyclic guanosine monophosphate (cGMP) to 5'-GMP. This leads to increased intracellular cGMP concentrations, which activates protein kinase G (PKG), resulting in decreased intracellular calcium and subsequent relaxation of smooth muscle cells (StatPearls, NBK549843; PubMed, PMC3121214).