Bender Andrew T, Beavo Joseph A
Department of Pharmacology, The University of Washington Medical School, Health Sciences Building Box 357280, Seattle, WA 98195-7280, USA.
Neurochem Int. 2004 Nov;45(6):853-7. doi: 10.1016/j.neuint.2004.03.015.
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.
由于能够水解环磷酸鸟苷（cGMP）的环核苷酸磷酸二酯酶（PDEs）具有多样的调节和催化特性，细胞所表达的特定cGMP PDEs将决定cGMP信号的持续时间和强度。反过来，这又导致不同细胞类型和组织之间产生不同的细胞反应。因此，确定哪些cGMP PDEs在不同组织和细胞类型中表达，可能会增进我们对生理和病理过程的理解。大脑是一个在特定区域和细胞类型中表达大量不同cGMP PDEs的区域。一个恰当的例子是cGMP PDEs在神经元细胞中的差异表达。例如，我们最近发现PDE5在所有浦肯野神经元中表达，而PDE1B仅在这些神经元的一个子集中表达。PDE2的表达也被发现对离散的神经元群体具有选择性。cGMP PDE选择性表达的另一个例子见于细胞因子诱导单核细胞分化为巨噬细胞的过程。我们最近发现，用细胞因子巨噬细胞集落刺激因子（M-CSF）诱导单核细胞分化会导致PDE2上调，PDE1B略有增加，而粒细胞-巨噬细胞集落刺激因子（GM-CSF）会导致PDE1B大幅增加，但PDE2减少。这些相同的细胞因子可以影响小胶质细胞的表型，并且可能影响它们cGMP PDEs的表达。在本报告中，我们展示了我们实验室的最新结果，并回顾了早期的发现，阐述了cGMP PDEs高度特异性表达的概念，并讨论了这对于理解脑功能和功能障碍可能有多重要。
