cGMP-specific 3',5'-cyclic phosphodiesterase type 5A (PDE5A)

cGMP-specific 3',5'-cyclic phosphodiesterase type 5A (PDE5A) is a key enzyme responsible for the hydrolysis of cyclic guanosine monophosphate (cGMP) into 5'-GMP, thereby acting as a negative regulator of the nitric oxide (NO)/cGMP signaling pathway [1.2.1, 1.3.1]. It is predominantly expressed in the smooth muscle cells of the corpus cavernosum, vascular system, and lungs, where it modulates vascular tone and blood flow [1.2.2, 1.3.3]. By degrading cGMP, PDE5A terminates the signal for smooth muscle relaxation, making it a critical target in conditions characterized by impaired vasodilation [1.2.3, 1.4.5]. Pharmacological inhibition of PDE5A by drugs such as sildenafil and tadalafil increases intracellular cGMP levels, enhancing the vasodilatory effects of nitric oxide [1.2.2, 1.2.5]. This mechanism is therapeutically exploited for the treatment of erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia [1.2.3, 1.4.5]. Beyond its established roles, PDE5A is also implicated in cardiac remodeling and heart failure, where its upregulation is associated with pathological hypertrophy [1.1.3, 1.4.1].

Other names

PDE5CGB-PDEcGMP-binding cGMP-specific phosphodiesteraseCN5APhosphodiesterase isozyme 5

Competitive inhibition of the PDE5A catalytic site, preventing the hydrolysis of cGMP to 5'-GMP, which increases intracellular cGMP levels and enhances nitric oxide-mediated smooth muscle relaxation.