Table 2.

Physiological and/or functional roles of PDEs

PDE family	Role(s)	Evidence*
1	Vascular smooth muscle proliferation; Ca2+ modulation of olfaction	Broad distribution, but highest levels in proliferating vascular smooth muscle cells, testes, heart and neural tissues (for example, olfactory epithelial cells). Binding and inactivation by Ca2+/calmodulin
2	Regulation of Ca2+ channels, olfaction, platelet aggregation and aldosterone secretion	Broad distribution, but highest levels in brain and adrenal cortex197
3	Cardiac contractility, insulin secretion and lipolysis	Broad distribution, but particular abundance in adipose tissue, liver, cardiac muscle, vascular smooth muscle and platelets; inhibited by drugs with cardiotonic, vasodilatory, thrombolytic, and antiplatelet aggregation properties. Stimulated by insulin, leptin and insulin-like growth factor198
4	Immunological and inflammatory signalling processes; smooth muscle tone; depression	Broad distribution, highest levels in neural and endocrine tissue. Inflammatory cells thought to participate in the pathogenesis of inflammatory diseases (such as asthma and chronic obstructive pulmonary disease) preferentially express PDE4
5	Penile erection; smooth muscle tone of vasculature, airways and gastrointestinal tract	Abundant distribution in smooth muscle. The PDE5-specific inhibitor sildenafil has clinical efficacy for the treatment of erectile dysfunction
6	Vision	Distribution in rod and cone photoreceptor cells. Some visual defects are related to PDE6 mutations
7	T-lymphocyte activation and proliferation; skeletal muscle metabolism	Distribution is predominantly in T lymphocytes (PDE7A1). PDE7 mRNA is abundant in skeletal muscle tissue, T lymphocytes and B lymphocytes, but protein and activity are readily measurable only in T lymphocytes
8	T-cell activation	PDE8A mRNA is widely expressed (highest in testis). PDE8B is unique to the thyroid gland199
9	Possibly maintains basal intracellular cGMP levels or natriuresis and vascular tone	mRNA is widely expressed, particularly in spleen, intestine, kidney, heart and brain
10	Unknown	Human PDE10 is widely distributed
11	Sperm capacitation; other functions unknown	mRNA occurs at highest levels in skeletal muscle, prostate, kidney, liver, pituitary and salivary glands, and testis. Protein is localized to vascular smooth muscle cells, cardiac myocytes, corpus cavernosum of the penis, prostate and skeletal muscle
*See Refs 191–196. cGMP, cyclic guanosine monophosphate; PDE, phosphodiesterase.