phosphodiesterase3

Phosphodiesterase 3 (PDE3) refers to a subfamily of cyclic nucleotide phosphodiesterases that catalyze the breakdown of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). The PDE3 family includes two main genes, PDE3A and PDE3B, which produce the enzyme isoforms PDE3A and PDE3B. These enzymes are expressed in multiple tissues, with PDE3A found prominently in platelets, cardiac tissue, and vascular smooth muscle, and PDE3B enriched in adipose tissue, liver, and some other tissues.

Catalytic properties and regulation: PDE3 enzymes hydrolyze both cAMP and cGMP, though they have a higher affinity for cAMP. cGMP can act as an allosteric regulator by inhibiting PDE3, thereby reducing cAMP breakdown in certain cellular contexts. This cross-talk between cAMP and cGMP signaling allows PDE3 to modulate responses such as heart muscle contraction, vascular tone, and platelet aggregation.

Biological roles: In the heart, PDE3 regulates contractility by influencing cAMP-dependent signaling. In platelets, PDE3 activity reduces cAMP levels and promotes aggregation; in vascular smooth muscle, PDE3 influences vasomotor tone; in adipocytes, it affects lipolysis. The enzyme thus participates in cardiovascular regulation, hemodynamics, and energy metabolism.

Clinical relevance: PDE3 inhibitors, such as milrinone and enoximone, are used as positive inotropes in acute decompensated heart failure. Cilostazol is a selective PDE3 inhibitor used to treat intermittent claudication by improving blood flow and reducing platelet aggregation. Inhibition of PDE3 can cause side effects including arrhythmias, hypotension, and GI symptoms, and interactions with other vasoactive drugs are considered in clinical use.

The enzyme is encoded by PDE3A and PDE3B genes and functions as a key modulator of cyclic nucleotide signaling across several tissues.