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

cGMP-inhibited 3',5'-cyclic phosphodiesterase 3 (PDE3) is an enzyme family responsible for the breakdown of cyclic adenosine monophosphate (cAMP) and, to a lesser extent, cyclic guanosine monophosphate (cGMP) [1][2]. It is distinctively characterized by its high affinity for both cAMP and cGMP, where cGMP acts as a potent competitive inhibitor of cAMP hydrolysis [3]. The target name provided, 'cGMP-specific phosphodiesterase 3', is technically incorrect as PDE3 is defined by its inhibition by cGMP, whereas 'cGMP-specific' refers to other families like PDE5 [4]. PDE3 exists as two isoforms: PDE3A, primarily found in the heart, platelets, and vascular smooth muscle, and PDE3B, found in adipocytes and hepatocytes [1][2][4]. By regulating cAMP levels, PDE3 plays a critical role in cardiac contractility, vascular tone, and platelet activation [3][6]. Drugs targeting PDE3, such as milrinone and cilostazol, are used to treat acute heart failure and intermittent claudication, respectively [4][5]. However, their use is often limited by risks of arrhythmias and increased mortality with long-term administration in heart failure patients [5][6].

Other names

PDE3cGMP-inhibited phosphodiesteraseCyclic nucleotide phosphodiesterase 3Phosphodiesterase 3

PDE3 inhibitors block the hydrolysis of cAMP, leading to increased intracellular cAMP concentrations. In cardiomyocytes, this increases calcium influx and contractility; in vascular smooth muscle and platelets, it promotes relaxation and inhibits aggregation [3][4].