In general, the action of intracellular second messengers, 3′:5′-cyclic adenosine monophosphate (cAMP) and 3′:5′-cyclic guanosine monophosphate (cGMP), are terminated by cyclic nucleotide phosphodiesterase (PDE). In most mammalian tissues, PDE exists in multiple forms that differ in subcellular localization, catalytic, regulatory, and immunological properties (1 –4 ). One of these forms of enzyme is activated by Ca2+ and calmodulin (CaM) and has a lower apparentKmfor cGMP than for cAMP and higherVmax for cAMP than for cGMP (2 ,5 ,6 ). This CaM-dependent cyclic nucleotide phosphodiesterase (CaMPDE) is widely distributed among mammalian tissues and other eukaryotes (7 –11 ). CaMPDE is one of the most intensively studied and best characterized PDEs (12 –19 ).
