Specific localized expression of cGMP PDEs in Purkinje neurons and macrophages.

As cGMP hydrolyzing cyclic nucleotide phosphodiesterases (PDEs) have diverse regulatory and catalytic properties, the specific cGMP PDEs a cell expresses will determine the duration and intensity of a cGMP signal. This, in turn, results in different cellular responses between cell types and tissues. Therefore, identifying which cGMP PDEs are expressed in different tissues and cell types could increase our understanding of physiological and pathological processes. The brain is one area where large numbers of diverse cGMP PDEs are expressed in specific regions and cell types. A case in point is differential expression of cGMP PDEs in neuronal cells. For example, we have recently found that PDE5 is expressed in all Purkinje neurons while PDE1B is expressed in only a subset of these neurons. The expression of PDE2 has also been found to be selective for discrete populations of neurons. Another example of selective cGMP PDE expression is seen with cytokine-induced differentiation of monocytes to macrophages. We have recently discovered that monocyte differentiation with the cytokine macrophage colony-stimulating factor (M-CSF) causes an upregulation of PDE2 and a small increase in PDE1B while granulocyte-macrophage colony-stimulating factor (GM-CSF) causes a large increase in PDE1B but a decrease in PDE2. These same cytokines can influence the phenotype of microglial cells and are likely to affect their expression of cGMP PDEs. In this report, we present recent results from our laboratory and review earlier findings illustrating the concept of highly specific expression of cGMP PDEs and discuss how this may be important for understanding brain function and dysfunction.