The phosphodiesterase (PDE) superfamily

PDE familyLocalisationSubstrate specificityMain functionsReferences
PDE1Widely distributed; adipose, brain, kidney, heart, skeletal muscle, testes and thyroidcAMP
Vascular smooth muscle contraction, sperm function, dopaminergic signalling, immune cell activation[7681]
PDE2Widely distributed; significant in the brain, heart (myocytes), liver, adrenal cortex, endothelium and plateletscAMP
Regulates aldosterone secretion, phosphorylation of calcium channels in heart, cGMP in neurons; endothelial cell function under inflammatory conditions[79, 8284]
PDE3Widely distributed; significant in cardiac and vascular myocytes, brain, liver, adipose tissues, pancreatic β-cells, endothelium, epithelium, oocytes and plateletscAMP
Cardiac contractility, platelet aggregation, vascular smooth muscle contraction, oocyte maturation, renin release, insulin signalling, cell cycle/proliferation[8590]
PDE4Widely distributed; significant in cells of the cardiovascular, neural, immune and inflammatory systemscAMPBrain function, monocyte and macrophage activation, neutrophil infiltration, vascular smooth muscle proliferation, fertility, vasodilation, cardiac contractility[9093]
PDE5Widely distributed; significant in vascular myocytes, diseased cardiac myocytes, lung, brain, platelets, kidney, gastrointestinal tissues and peniscGMPVascular smooth muscle contraction, platelet aggregation, cGMP signalling in brain[9497]
PDE6Expression limited to photoreceptors and pineal glandcGMPPhototransduction[98, 99]
PDE7Widely distributed, including brain, heart, liver kidney, placenta and lymphoid tissuescAMPImmune cell activation, memory[100102]
PDE8Widely distributed, with high expression in adipose tissue, brain, kidney, testes and thyroidcAMPT-cell activation, sperm or Leydig cell function, T4 and T3 production[103105]
PDE9Brain, heart, adipose tissue and livercGMPNO-cGMP signalling in brain[106108]
PDE10Expression limited to brain and testescAMP
Learning and memory[79, 109111]
PDE11Expression predominantly in prostate, testes and skeletal musclecAMP
Sperm development and function[111, 112]

cGMP: cyclic guanosine monophosphate; NO: nitric oxide.