Properties of cyclic nucleotide PDE families
| PDE Family | Cyclic Nucleotide Substrates | Inhibitors (Ki) | No. of Genes | Regulation |
|---|---|---|---|---|
| PDE1: Ca2+/CAM stimulated PDE | cAMP and cGMP | Vinpocetine (14 μM), W-7 (300 μM) | 3 | (+) Ca2+/CAM (-) PKA, CamKII |
| PDE2: cGMP-stimulated PDE | cAMP and cGMP | EHNA (1 μM) | 1 | (+) cGMP, PKC (+/-) N-terminal targeting domain |
| PDE3: cGMP-inhibited PDE | cAMP > cGMP | Cilostamide (20 nM), milrinone (150 nM), zardaverine (IC50 0.5-2 μM) | 2 | (+) PKA, PKB (-) cGMP (+/-) N-terminal targeting domain |
| PDE4: High affinity, Rolipram-sensitive cAMP-specific PDE | cAMP | Rolipram (1 μM), Ro 20-1724 (5 μM), piclamilast (1 nM), zardaverine (IC50 0.8-4 μM) | 4 | (+) PKA, ERK, Phosphatidic Acid (-) ERK, Caspases (+/-) N-terminal targeting domains |
| PDE5: cGMP-specific PDE | cGMP | Zaprinast (130 nM), sildenafil (10 nM), vardenafil (1 nM), tadalafil (10 nM) | 1 | (+) cGMP, PKG, PKA (-) Caspases |
| PDE6: Photoreceptor cGMP-specific PDE | cGMP | Zaprinast (400 nM), dipyridamole (125 nM), sildenafil (50 nM) | 3 | (+) Trasnsducin (-) cGMP, gamma and delta subunits |
| PDE7: High-affinity, Rolipram-insensitive cAMP-specific PDE | cAMP | IBMX (4 μM), dipyridamole (600 nM) | 2 | (+/-) PKA |
| PDE8: High-affinity and IBMX-insensitive cAMP-specific PDE | cAMP | Dipyridamole (9 μM) | 2 | PAS domain |
| PDE9: High-affinity cGMP-specific PDE | cGMP | Zaprinast (35 μM) | 1 | |
| PDE10: cAMP-Inhibited cGMP PDE | cAMP < cGMP | Dipyridamole (1 μM), | 1 | (-) cAMP |
| PDE11: Dual specificity cGMP-binding PDE | cAMP and cGMP | Zaprinast (12 μM), dipyridamole (0.4 μM), tadalafil (60 μM) | 1 |
W7, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; EHNA, erythro-9-(2-hydroxy-3-nonyl)adenine; IBMX, 3-isobutyl-1-methylxanthine; Ca2+/CAM, calcium/calmodulin.