Fosfodiesteraser

Fosfodiesteraser, commonly called phosphodiesterases (PDEs), are enzymes that hydrolyze phosphodiester bonds in nucleic acids and, most importantly, in cyclic nucleotide monophosphates such as cAMP and cGMP, thereby regulating intracellular signaling. In humans, PDEs are categorized into 11 gene families (PDE1–PDE11), each with distinct catalytic domains, tissue distribution, regulation, and substrate preference. The catalytic domain requires divalent metal ions, typically Mg2+ and/or Mn2+; many PDEs are regulated by calcium/calmodulin or phosphorylation.

PDEs differ in substrate specificity: some prefer cAMP (e.g., PDE4); some prefer cGMP (e.g., PDE5, PDE9); others hydrolyze both (e.g., PDE3, PDE10, PDE11). PDE6 is retina-specific and important for phototransduction. Tissue expression varies: PDE5 is enriched in vascular smooth muscle; PDE4 predominates in inflammatory and immune cells; PDE3 in platelets and cardiac muscle.

Clinically, PDEs are targets for a range of therapies. PDE inhibitors raise cAMP/cGMP levels and cause smooth muscle relaxation or anti-inflammatory effects. Examples include sildenafil, tadalafil, vardenafil (PDE5 inhibitors) for erectile dysfunction and pulmonary hypertension; roflumilast (PDE4 inhibitor) for COPD; milrinone and inamrinone (PDE3 inhibitors) used in acute heart failure. Caffeine and theophylline are nonselective PDE inhibitors.

See also: phosphodiesterase inhibitors.