cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (PDE3A) (PDE3A)

cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (PDE3A) is a member of the phosphodiesterase enzyme family that regulates intracellular signaling by hydrolyzing the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). It is uniquely characterized by its high affinity for both cAMP and cGMP, with cGMP acting as a potent competitive inhibitor of cAMP hydrolysis. PDE3A is predominantly expressed in the myocardium, vascular smooth muscle, and platelets, where it plays a critical role in controlling cardiac contractility, blood vessel tone, and platelet activation. In the heart, inhibition of PDE3A increases cAMP levels, which enhances calcium influx and promotes cardiac contraction (inotropy) and relaxation (lusitropy). Consequently, PDE3A is a significant therapeutic target for drugs like milrinone and cilostazol, used to treat acute heart failure and peripheral vascular disease. Beyond its cardiovascular roles, recent research has identified PDE3A as a participant in pro-apoptotic pathways in certain cancers when it forms a complex with the protein Schlafen 12 (SLFN12).

Other names

cGMP-inhibited 3',5'-cyclic phosphodiesterase APhosphodiesterase 3ACGI-PDE AcGI-PDEcGMP-inhibited cAMP phosphodiesterasecGIP1

Selective catalytic inhibition of the phosphodiesterase 3 enzyme, leading to decreased breakdown and subsequent accumulation of intracellular cAMP and cGMP.