TABLE 1

The phosphodiesterase (PDE) superfamily

PDE family	Localisation	Substrate specificity	Main functions	References
PDE1	Widely distributed; adipose, brain, kidney, heart, skeletal muscle, testes and thyroid	cAMP cGMP	Vascular smooth muscle contraction, sperm function, dopaminergic signalling, immune cell activation	[76–81]
PDE2	Widely distributed; significant in the brain, heart (myocytes), liver, adrenal cortex, endothelium and platelets	cAMP cGMP	Regulates aldosterone secretion, phosphorylation of calcium channels in heart, cGMP in neurons; endothelial cell function under inflammatory conditions	[79, 82–84]
PDE3	Widely distributed; significant in cardiac and vascular myocytes, brain, liver, adipose tissues, pancreatic β-cells, endothelium, epithelium, oocytes and platelets	cAMP cGMP	Cardiac contractility, platelet aggregation, vascular smooth muscle contraction, oocyte maturation, renin release, insulin signalling, cell cycle/proliferation	[85–90]
PDE4	Widely distributed; significant in cells of the cardiovascular, neural, immune and inflammatory systems	cAMP	Brain function, monocyte and macrophage activation, neutrophil infiltration, vascular smooth muscle proliferation, fertility, vasodilation, cardiac contractility	[90–93]
PDE5	Widely distributed; significant in vascular myocytes, diseased cardiac myocytes, lung, brain, platelets, kidney, gastrointestinal tissues and penis	cGMP	Vascular smooth muscle contraction, platelet aggregation, cGMP signalling in brain	[94–97]
PDE6	Expression limited to photoreceptors and pineal gland	cGMP	Phototransduction	[98, 99]
PDE7	Widely distributed, including brain, heart, liver kidney, placenta and lymphoid tissues	cAMP	Immune cell activation, memory	[100–102]
PDE8	Widely distributed, with high expression in adipose tissue, brain, kidney, testes and thyroid	cAMP	T-cell activation, sperm or Leydig cell function, T4 and T3 production	[103–105]
PDE9	Brain, heart, adipose tissue and liver	cGMP	NO-cGMP signalling in brain	[106–108]
PDE10	Expression limited to brain and testes	cAMP cGMP	Learning and memory	[79, 109–111]
PDE11	Expression predominantly in prostate, testes and skeletal muscle	cAMP cGMP	Sperm development and function	[111, 112]

cGMP: cyclic guanosine monophosphate; NO: nitric oxide.