Phosphodiesterase (specifically cyclic nucleotide phosphodiesterase) (PDE)

Phosphodiesterases are a superfamily of enzymes that catalyze the hydrolysis of the phosphodiester bond in cyclic nucleotides, primarily cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby regulating the amplitude and duration of intracellular signaling events. There are 11 families encoded by 21 genes, many with numerous isoforms, allowing tissue- and function-specific regulation of cAMP/cGMP signaling. Inhibition of phosphodiesterases (by drugs such as caffeine, theophylline, or selective synthetic inhibitors) elevates cyclic nucleotide concentrations and is the basis for treatments in erectile dysfunction, cardiac failure, respiratory and inflammatory diseases, as well as neurological disorders. The target “Caffeine + Phosphodiesterase” is a conceptual error—caffeine is a nonselective, relatively weak inhibitor of several PDE isoforms (including PDE1, 4, and 5), not a molecular target itself.

Other names

Cyclic nucleotide phosphodiesterasePDEcAMP phosphodiesterasecGMP phosphodiesterasePDE1–PDE11 (individual subfamily designations)

Competitive or noncompetitive inhibition of phosphodiesterase active site, resulting in elevated intracellular cAMP and/or cGMP. Prevents cyclic nucleotide breakdown, leading to smooth muscle relaxation, vasodilation, bronchodilation, and altered cellular signaling.