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Phosphodiesterase 3, often abbreviated as PDE3, is a family of enzymes belonging to the phosphodiesterase (PDE) superfamily. These enzymes are crucial regulators of intracellular cyclic nucleotide signaling, specifically cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE3 enzymes hydrolyze these cyclic nucleotides, thereby terminating their signaling pathways and reducing their cellular concentrations.

There are two main isoforms of PDE3: PDE3A and PDE3B. PDE3A is predominantly found in cardiac and smooth muscle cells, where it plays a significant role in modulating contractility and vascular tone. In the heart, PDE3A's inhibition leads to increased cAMP levels, which enhances cardiac contractility and heart rate. In vascular smooth muscle, PDE3A contributes to vasodilation by promoting smooth muscle relaxation. PDE3B is primarily expressed in adipose tissue and the liver, where it regulates lipolysis and glycogenolysis, respectively, by influencing cAMP levels.

Dysregulation of PDE3 activity has been implicated in various physiological and pathological conditions. For instance, inhibitors of PDE3, such as milrinone and cilostazol, are used clinically to treat heart failure and intermittent claudication, respectively, due to their positive inotropic and vasodilatory effects. Conversely, impaired PDE3 function can contribute to cardiovascular diseases. Research continues to explore the broader roles of PDE3 in cellular processes and its potential as a therapeutic target for a range of disorders.