Summary of the data on the contribution of different mechanisms to cAMP compartmentalization
| Cell type | AC (cAMP synthesis) | PDE (cAMP degradation) | Hindered diffusion | Cell shape | cAMP buffers | Notes | References |
| HEK293 cells | ND | Yes: PDE inhibition abolishes differences cytosol/membrane | Yes | ND | Yes | Modified CNG channel | Rich et al. (2000, 2001, 2007) |
| HEK293 cells | ND | Yes: Loss of gradient with PDE4 RNAi; no effect of PDE4 inhibitors | No: Computational analysis | ND | ND | PKA/EPAC reporters | Terrin et al. (2006); Oliveira et al. (2010) |
| HEK293 cells | Yes (targeted AC8) | Yes: Loss of membrane compartment after PDE4 inhibition | ND | ND | ND | Gravin-mediated complex | Willoughby et al. (2006) |
| MEFs | ND | No: PDE4B ablation increases cytosol/membrane gradient | ND | ND | ND | CNGC/EPAC reporters | Blackman et al. (2011) |
| Neonatal cardiac myocytes | ND | Yes: IBMX abolishes local cAMP accumulation | ND | ND | ND | PKA reporter | Zaccolo and Pozzan (2002); Mongillo et al. (2004) |
| Neonatal cardiac myocytes | Yes (receptor-dependent βAR vs. PGE2) | Yes: PDE inhibition decreases the PKA-phosphorylation gradients | Yes | ND | Yes | Membrane/cytosol restricted diff. local cAMP uncaging | Saucerman et al. (2006) |
| Neurons (dendrites) | Yes: Role of negative regulatory loop | No | Yes: Dendrite diameter | Bacskai et al. (1993); Neves et al. (2008) | |||
| Adult cardiac myocytes | Differences β1/β2 responses | No: No PDE effect on diffusion of the β2AR restricted signal | Yes | ND | ND | HCN2-cAMP probe in transgenic mice | Nikolaev et al. (2006) |
| Vascular endothelium | Yes: Membrane vs. cytosol AC | Yes: PDE4D4 displacement affects membrane cAMP; Rolipram disrupts the gradient | Yes | Yes | Yes | Manipulation of site of cAMP synthesis | Sayner et al. (2006); Feinstein et al. (2012) |
| Cell type | AC (cAMP synthesis) | PDE (cAMP degradation) | Hindered diffusion | Cell shape | cAMP buffers | Notes | References |
| HEK293 cells | ND | Yes: PDE inhibition abolishes differences cytosol/membrane | Yes | ND | Yes | Modified CNG channel | Rich et al. (2000, 2001, 2007) |
| HEK293 cells | ND | Yes: Loss of gradient with PDE4 RNAi; no effect of PDE4 inhibitors | No: Computational analysis | ND | ND | PKA/EPAC reporters | Terrin et al. (2006); Oliveira et al. (2010) |
| HEK293 cells | Yes (targeted AC8) | Yes: Loss of membrane compartment after PDE4 inhibition | ND | ND | ND | Gravin-mediated complex | Willoughby et al. (2006) |
| MEFs | ND | No: PDE4B ablation increases cytosol/membrane gradient | ND | ND | ND | CNGC/EPAC reporters | Blackman et al. (2011) |
| Neonatal cardiac myocytes | ND | Yes: IBMX abolishes local cAMP accumulation | ND | ND | ND | PKA reporter | Zaccolo and Pozzan (2002); Mongillo et al. (2004) |
| Neonatal cardiac myocytes | Yes (receptor-dependent βAR vs. PGE2) | Yes: PDE inhibition decreases the PKA-phosphorylation gradients | Yes | ND | Yes | Membrane/cytosol restricted diff. local cAMP uncaging | Saucerman et al. (2006) |
| Neurons (dendrites) | Yes: Role of negative regulatory loop | No | Yes: Dendrite diameter | Bacskai et al. (1993); Neves et al. (2008) | |||
| Adult cardiac myocytes | Differences β1/β2 responses | No: No PDE effect on diffusion of the β2AR restricted signal | Yes | ND | ND | HCN2-cAMP probe in transgenic mice | Nikolaev et al. (2006) |
| Vascular endothelium | Yes: Membrane vs. cytosol AC | Yes: PDE4D4 displacement affects membrane cAMP; Rolipram disrupts the gradient | Yes | Yes | Yes | Manipulation of site of cAMP synthesis | Sayner et al. (2006); Feinstein et al. (2012) |