3',5'-cyclic nucleotide phosphodiesterase (PDE)

3',5'-Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes (EC 3.1.4.17) comprising 11 families (PDE1-PDE11) with multiple isoforms that hydrolyze 3',5'-cyclic nucleotides like cAMP and cGMP into inactive 5'-monophosphates, thereby regulating intracellular levels of these critical second messengers and terminating signaling cascades. They play key roles in diverse physiological processes, including signal transduction in cardiac myocytes, visual phototransduction (PDE6), platelet aggregation (PDE3), airway smooth muscle relaxation (PDE4/5), and neuronal functions. Dysregulation contributes to diseases such as COPD/asthma (PDE4), erectile dysfunction/pulmonary hypertension (PDE5), heart failure (PDE3/5), and cancers where elevated cAMP/cGMP promotes proliferation. Selective inhibitors like sildenafil (PDE5) and roflumilast (PDE4) are approved therapeutics that boost cyclic nucleotide signaling for vasodilation, anti-inflammatory effects, and bronchodilation, while isoform-specific targeting minimizes off-target effects. Challenges include isoform diversity, tissue-specific expression, and side effects like gastrointestinal upset from PDE4 inhibition.

Other names

cyclic nucleotide phosphodiesterase3',5'-cyclic-nucleotide 5'-nucleotidohydrolasephosphodiesterases (PDE1-PDE11)

Inhibition of cyclic nucleotide hydrolysis to elevate cAMP or cGMP levels, Reversible competitive inhibition