Phosphodiesterase 5A (PDE5A) (PDE5A)

Phosphodiesterase 5A (PDE5A) is a homodimeric enzyme that specifically catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a secondary messenger crucial for smooth muscle relaxation and vasodilation (UniProt P53667). It is predominantly expressed in the corpus cavernosum, vascular smooth muscle, platelets, and the lungs (PubMed: 15082007). By regulating cGMP levels, PDE5A plays a pivotal role in the nitric oxide (NO)/cGMP signaling pathway, which mediates the physiological response to sexual stimulation and regulates pulmonary vascular resistance (StatPearls: NBK549843). Dysregulation or overactivity of PDE5A is associated with conditions such as erectile dysfunction and pulmonary arterial hypertension (PAH). Pharmacological inhibition of PDE5A by drugs like sildenafil and tadalafil increases intracellular cGMP, promoting vasodilation and improving clinical outcomes in these diseases (NIH: PMC3130794). However, its use is strictly contraindicated with nitrates due to the risk of severe, potentially fatal hypotension, and it has been linked to rare sensory side effects like non-arteritic anterior ischemic optic neuropathy (NAION) (FDA Label: Viagra). Beyond its primary indications, PDE5A is also investigated for roles in cardiac remodeling and neuroprotection, making it a versatile target in cardiovascular and metabolic medicine.

Other names

cGMP-binding cGMP-specific 3',5'-cyclic phosphodiesterasePhosphodiesterase 5PDE5Phosphodiesterase type 5CGB-PDE

Competitive inhibition of the catalytic site of PDE5, preventing the hydrolysis of cGMP to 5'-GMP, thereby increasing intracellular cGMP levels and enhancing the nitric oxide (NO)-mediated relaxation of smooth muscle.