ABSTRACT
A single Phosphodiesterase-2 (PDE2) variant, PDE2A, is expressed in cardiac tissues and isolated cardiomyocytes of several species, including rat and human. Probably the first evidence for a contribution of PDEs to intracellular cyclic nucleotide compartmentation comes from a study in guinea pig perfused hearts. The level of intracellular 3',5'-cyclic adenosine monophosphate (cAMP) is regulated by the balance between the activity of adenylate cyclase and the cyclic nucleotide PDEs that degrade cAMP to 5' adenosine monophosphate. Intracardiac cyclic guanosine monophosphate (cGMP) acts via three main enzymes: PDE2, PDE3, and cGMP-dependent protein kinase. A final example of a complex around a PDE4 isoform in heart is the one formed by PDE4D5 and β-arrestins. PDE5 is highly expressed in vascular smooth muscle, and its inhibition is a primary target for the treatment of erectile dysfunction and pulmonary hypertension. In many examples, more than one PDE isoform is involved in controlling the cAMP or cGMP concentration at any given intracellular location inside a cardiomyocyte.
