ABSTRACT
The ligand-free crystal structure of the human Phosphodiesterase-2 (PDE2) catalytic domain showed it to be similar to that of other published PDE domains. The role of PDE2 in endothelial cell function is an area of intense interest. An interesting phenomenon is the apparent stimulation of PDE2 activity by low concentrations of certain compounds normally thought to be competitive inhibitors. The physiological roles of and the signaling pathways regulated by PDE2 are slowly beginning to be deciphered. The original determination of the boundaries of the PDE2 catalytic domain, and regulatory segment containing GAFs, was deduced through amino acid sequence comparisons and photolabeling experiments. The PDE3 inhibitors, motapizone and cilostamide, both raised cyclic adenosine monophosphate (cAMP) and inhibited release of serotonin from thrombin-activated platelets, which was not affected by treatment with PDP, a PDE2 inhibitor. In rat ventricular fibroblasts, nitric oxide-stimulated cyclic guanine monophosphate production mediates most of the effects of interleukin-1β on cAMP accumulation, in large part by activating PDE2.
