Immunohistochemical Localization of Phosphodiesterase 2A in Multiple Mammalian Species

Abstract

Phosphodiesterases (PDEs) comprise a family of enzymes that regulate the levels of cyclic nucleotides, key second messengers that mediate a diverse array of functions. PDE2A is an evolutionarily conserved cGMP-stimulated cAMP and cGMP PDE. In the present study, the regional and cellular distribution of PDE2A in tissues of rats, mice, cynomolgus monkeys, dogs, and humans was evaluated by immunohistochemistry. A polyclonal antibody directed to the C-terminal portion of PDE2A specifically detected PDE2A by Western blotting and by immunohistochemistry. The pattern of PDE2A immunoreactivity (ir) was consistent across all species. Western blot analysis demonstrated that PDE2A was most abundant in the brain relative to peripheral tissues. PDE2A ir was heterogeneously distributed within brain and was selectively expressed in particular peripheral tissues. In the brain, prominent immunoreactivity was apparent in components of the limbic system, including the isocortex, hippocampus, amygdala, habenula, basal ganglia, and interpeduncular nucleus. Cytoplasmic PDE2A staining was prominent in several peripheral tissues, including the adrenal zona glomerulosa, neurons of enteric ganglia, endothelial cells in all organs, lymphocytes of spleen and lymph nodes, and pituitary. These studies suggest that PDE2A is evolutionarily conserved across mammalian species and support the hypothesis that the enzyme plays a fundamental role in signal transduction.

First-in-Human Assessment of the Novel PDE2A PET Radiotracer 18F-PF-05270430

“…Western blot analysis of human brain extracts with anti-PDE2A antibodies revealed that PDE2A immunoreactivity was prominently observed in the striatum, cingulate cortex, prefrontal cortex, and hippocampus, with no detectable signal in the cerebellum (4). A blocking study in humans would be needed to validate the suitability of the cerebellum as a reference region.…”

“…In non-central nervous system tissues, PDE2A is highly expressed in adrenal glands and vascular endothelial cells in which it may regulate vascular permeability (4). The development of a PDE2A radioligand would allow the evaluation of disease-specific changes (e.g., in schizophrenia) and potential inhibitor drugs.…”

Synthesis, 18F-Radiolabelling and Biological Characterization of Novel Fluoroalkylated Triazine Derivatives for in Vivo Imaging of Phosphodiesterase 2A in Brain via Positron Emission Tomography

“…In vitro autoradiographic studies were accomplished by incubating sagittal sections of rat brain with [ , which is consistent with the distribution pattern of PDE2A protein in rat brain [9,11]. Therefore, we assume that the novel radioligands might be appropriate for in vitro imaging of PDE2A.…”

“…The PDE2A protein is highly and specifically expressed in particular brain regions such as striatum, cortex, hippocampus, substantia nigra, amygdala, and in olfactory neurons [9][10][11][12].…”

AIP and its interacting partners

“…This enzyme thus contributes to the crosstalk between these two second messenger pathways (Zaccolo & Movsesian 2007). PDE2A is strongly expressed in the brain with a moderate presence in peripheral tissues such as the adrenal gland and heart and skeletal muscle (Rosman et al 1997, Sadhu et al 1999, Stephenson et al 2009. In addition, PDE2A expression has been observed in rat (Velardez et al 2000, Stephenson et al 2009) and human pituitary (Lennox et al 2011).…”