Table 1.
Main characteristics of phosphodiesterase families, corresponding substrates and specific inhibitors, and their clinical applications.
| PDE | Main substrate | Km (μM) cAMP | Km (μM) GMP | Tissue expression | Specific inhibitors | Reference |
|---|---|---|---|---|---|---|
| 1 | Ca2 + / calmodulin-stimulated cAMP ≤ cGMP | 70–120 | 0.6–6.0 | Heart, brain, lung, smooth muscle, T lymphocytes, sperm | KS505a, bepril, Vinpocetine, Flunarizine, Amiodaronea,b | Bender and Beavo (2006), Yan et al. (1995), Loughney et al. (1996), Yu et al. (1997), Ahn et al. (1991), Medina et al. (2006), Menniti et al. (2006), Truss et al. (2001), Zhang et al. (2004), Jeon et al. (2010), Reed et al. (2002), Filgueiras et al. (2010), Medina (2010) |
| 2 | cAMP = cGMP | 30 | 10–24 | Adrenal gland, heart, lung, liver, platelets | EHNA, BAY 60–7550, Oxindole, PDPc | Rosman et al. (1997), Rivet-Bastide et al. (1997), Sadhu et al. (1999), Suvarna and O’Donnell (2002), Podzuweit et al. (1995), Repaske et al. (1992), Boess et al. (2004), Rutten et al. (2009) |
| 3 | cAMP > cGMP | 0.2–0.4 | 0.02–0.2 | Heart, lung, liver, kidney, oocytes, adipocytes, T lymphocytes, platelets, inflammatory cells | Cilostamide, Cilostazol, Enoxamone, Milrinone, Siguazodanb,d | Palmer and Maurice (2000), Vandecasteele et al. (2001), Shin et al. (2007), Nohria et al. (2003), Carev et al. (2010) |
| 4 | cAMP | 1.5–10 | – | Kidney, brain, liver, lung, smooth muscle, cardiovascular tissues, Sertoli cells inflammatory cells | Rolipram, Roflumilast, Cilomilast, Drotaverine, ibudilastb,d,e | Tenor et al. (1995a,b,c), Essayan (2001), Scott et al. (1991), O’Byrne and Gauvreau (2009) |
| 5 | cGMP | 290 | 2.9–6.2 | Lung, platelets, vascular, smooth muscle | Sildenafil, Vardenafil, Tadalafil, Zaprinastb,d,e | Hamet and Coquil (1978), Coquil et al. (1980), Francis et al. (1980), Francis and Corbin (1988), Moncada and Martin (1993), Sebkhi et al. (2003), Ghofrani et al. (2006), Milligan et al. (2002), Nichols et al. (2002), Muirhead et al. (2002), Burgess et al. (2008), Klotz et al. (2001), Gresser and Gleiter (2002), Stark et al. (2001), Ormrod et al. (2002), Eardley and Cartledge (2002), Bella and Brock (2003), Staab et al. (2004), Brock (2003), Porst et al. (2003), Curran and Keating (2003), Corbin et al. (2005), Wharton et al. (2005), Prickaerts et al. (2002), Baratti and Boccia (1999) |
| 6 | cGMP | 610–700 | 15–17 | Photoreceptor | Dipyridamole | Zhang et al. (2005), Estrade et al. (1998) |
| 7 | cAMP | 0.03–0.2 | – | Skeletal muscle, heart, kidney, brain, pancreas, T lymphocytes, eosinophils, neutrophils | BRL-50481, BC30b | Gardner et al. (2000), Sasaki et al. (2000), Hetman et al. (2000a), Smith et al. (2003), Pitts et al. (2004), Vergne et al. (2004), Zhang et al. (2008) |
| 8 | cAMP | 0.06 | – | Testis, eye, liver, skeletal muscle, heart, kidney, ovary, brain, T lymphocytes | PF-04957325f | Perez-Torres et al. (2003), Wang et al. (2001), Hayashi et al. (2007), Kobayashi et al. (2003), Glavas et al. (2001), Dong et al. (2006), Vasta et al. (2006), Vang et al. (2010), Tsai et al. (2011), Dov et al. (2008) |
| 9 | cGMP | 230 | 0.2–0.7 | Kidney, liver, lung, brain, spleen, small intestine | BAY 73-6691 | Soderling et al. (1998a,b), van der Staay et al. (2008) |
| 10 | cAMP < cGMP | 0.2–1.0 | 13–14 | Testis, brain | pyrazoloquinoline analogs | Soderling et al. (1999), Fujishige et al. (1999), Loughney et al. (1999), Hebb et al. (2004), Yang et al. (2012) |
| 11 | cAMP = cGMP | 2.0–3.2 | 0.95–2.1 | Skeletal muscle, prostate, kidney, liver, pituitary, testis, salivary glands | BC 11-38 | Fawcett et al. (2000), Hetman et al. (2000b), Weeks et al. (2007), Ceyhan et al. (2012) |
aTherapeutic action with neuronal effects (neural plasticity, memory loss, detrusor instabilities, and urgency incontinence,…); bTherapeutic action with anti-inflammatory effects; cWithout therapeutic action; dtherapeutic action for lung diseases (asthma, COPD); eTherapeutic action with cardiovascular effects (inotopic, vasodilator,…); fTherapeutic action for adrenal insufficiency.