cGMP-inhibited 3',5'-cyclic phosphodiesterase (PDE3) (PDE3)

cGMP-inhibited 3',5'-cyclic phosphodiesterase, commonly known as PDE3, is a family of enzymes responsible for the hydrolysis and regulation of intracellular cyclic nucleotides, primarily cyclic adenosine monophosphate (cAMP) (Source: UniProt: Q14432). Although it can also hydrolyze cyclic guanosine monophosphate (cGMP), cGMP typically acts as a competitive inhibitor of the enzyme's cAMP-hydrolyzing activity at physiological concentrations (Source: PubMed: PMC2704133). The PDE3 family comprises two isoforms: PDE3A, which is predominantly expressed in the myocardium, vascular smooth muscle, and platelets, and PDE3B, which is found in adipocytes, hepatocytes, and pancreatic beta cells (Source: StatPearls: NBK559024). PDE3 is a significant therapeutic target because its inhibition raises cAMP levels, thereby increasing cardiac contractility (positive inotropy), inducing vasodilation, and inhibiting platelet aggregation (Source: NIH: PubChem). Clinical applications include the short-term treatment of acute decompensated heart failure and the management of intermittent claudication. However, long-term pharmacological inhibition of PDE3 in patients with chronic heart failure is associated with serious safety concerns, including a heightened risk of life-threatening arrhythmias and increased mortality (Source: PubMed: 11520182).

Other names

Phosphodiesterase 3cGIPDECyclic AMP phosphodiesterase 3PDE3APDE3B

Inhibition of the PDE3 enzyme prevents the hydrolysis of cyclic adenosine monophosphate (cAMP), leading to increased intracellular cAMP concentrations and the subsequent activation of protein kinase A (PKA) (Source: StatPearls: NBK559024; PubMed: PMC2704133).