cGMP-specific 3',5'-cyclic phosphodiesterase isoform 1 (PDE5A1) (PDE5A1)

cGMP-specific 3',5'-cyclic phosphodiesterase isoform 1 (PDE5A1) is a metallo-hydrolase enzyme that plays a central role in the regulation of the nitric oxide (NO)/cGMP signaling pathway by catalyzing the hydrolysis of cyclic guanosine monophosphate (cGMP) into 5'-GMP [2, 4, 8]. As the longest of the three splice variants of the PDE5A gene, PDE5A1 is ubiquitously expressed in tissues such as vascular smooth muscle, the lungs, and the corpus cavernosum [1, 5, 7]. By controlling intracellular cGMP levels, it acts as a critical regulator of smooth muscle relaxation, vasodilation, and platelet aggregation [3, 12, 14]. This enzyme is the primary therapeutic target for drugs like sildenafil and tadalafil, which are used to treat erectile dysfunction and pulmonary arterial hypertension by prolonging cGMP-mediated signaling [8, 10, 15]. Beyond these indications, PDE5A1 is implicated in the pathophysiology of heart failure, neurodegenerative diseases, and certain cancers, where its dysregulation contributes to impaired vasodilation and chronic inflammation [2, 7, 16]. Pharmacological inhibition of PDE5A1 is generally well-tolerated but carries significant risks, most notably severe hypotension when co-administered with organic nitrates [10, 15, 17].

Other names

Phosphodiesterase 5A isoform 1cGMP-binding cGMP-specific phosphodiesteraseCGB-PDEPDE5PDE5A

Competitive inhibition of the catalytic site of the enzyme, preventing the hydrolysis of cGMP to 5'-GMP, which leads to increased intracellular cGMP levels and subsequent activation of protein kinase G (PKG) [8, 10, 14].