Table 2.

Characteristics of the PDE Enzymes (4, 405)

Gene Family	Regulation	Substrate Specificity	Intracellular Localization	Main Functions	Ref.
PDE1	Ca2+/CaM-activated	cAMP, cGMP	Cytosolic	Vascular smooth muscle contraction, sperm function (PDE1A)	72, 82, 83, 406–408
				Dopaminergic signaling, immune cell activation, and survival (PDE1B)
				Vascular smooth muscle cell proliferation, sperm function, neuronal signaling (PDE1C)
PDE2	cGMP-activated	cAMP, cGMP	Membrane-bound or cytosolic	Regulates aldosterone secretion, phosphorylation of calcium channels in heart, cGMP in neurons; endothelial cell function under inflammatory conditions	47, 101, 406, 409
PDE3	cGMP-inhibited	cAMP, cGMP	Membrane-bound or cytosolic	Cardiac contractility, platelet aggregation, vascular smooth muscle contraction, oocyte maturation, renin release (PDE3A)	119, 395, 410–413
				Insulin signaling, cell cycle/proliferation (PDE3B)
PDE4	cGMP-insensitive	cAMP	Membrane-bound or cytosolic	Brain function, monocyte and macrophage activation, neutrophil infiltration, vascular smooth muscle proliferation, fertility, vasodilatation, cardiac contractility	395, 414–419
PDE5	PKA-PKG-phosphorylated	cGMP	Cytosolic	Vascular smooth muscle contraction, platelet aggregation, cGMP signaling in brain	406, 419–421
PDE6	cGMP-activated	cGMP	Cytosolic	Phototransduction	208, 422
PDE7	Rolipram-insensitive	cAMP	Cytosolic	Immune cell activation (PDE7A)	223, 423, 424
				Memory function and excreteT (PDE7B)
PDE8	cAMP-specific	cAMP	Membrane-bound or cytosolic	T-cell activation, sperm or Leydig cell function, T4 and T3 production (PDE8A)	239, 243, 250
PDE9	cGMP-specific	cGMP	Cytosolic or nuclear	NO-cGMP signaling in brain	260, 425
PDE10	Unknown	cAMP, cGMP	Cytosolic or particulate	Learning and memory	279, 281, 406
PDE11	Unknown	cAMP, cGMP	Cytosolic	Sperm development and function	16, 17, 426, 427

According to the most widely used consensus system, created in 1994 (428), the PDEs are named as follows: first, the abbreviation PDE, which denotes a 3′,5′ cyclic nucleotide PDE; second, an Arabic numeral referring to the gene family; third, a capital letter indicating the individual gene product according to the order of appearance in GenBank (ie, “A” usually, but not always, refers to the first member of the family reported; “B” refers to the second gene to be reported, etc); and finally, an Arabic number denoting the spliced variant. For instance, PDE10A1 stands for a PDE from family 10, the first identified gene, A, isoform 1.