ABSTRACT
Phosphodiesterases (PDEs) are a superfamily of enzymes that catalyze the hydrolysis of cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDEs are classi˜ed into 11 families (PDE1-11) based on their substrate speci˜cities, kinetics, allosteric regulators, and amino acid sequences (Beavo 1995; Conti and Beavo 2007; O’Donnell and Zhang 2004; Soderling and Beavo 2000). Each family is encoded by one to four genes, leading to a total of 21 PDE isoforms (Table 20.1). Based on their substrates, PDE families can be classi˜ed as cAMP-speci˜c (e.g., PDE4, PDE7, and PDE8), cGMP-speci˜c (e.g., PDE5, PDE6, and PDE9), or dual substrate (e.g., cAMP and cGMP) PDEs (e.g., PDE1, PDE2, PDE3, PDE10, and PDE11) (Beavo and Brunton 2002; Conti 2000; Francis et al. 2009; Mehats et al. 2002; Zhang 2009). PDEs contain
20.1 Introduction .......................................................................................................................... 419 20.2 Phosphodiesterase 2 .............................................................................................................. 421
20.2.1 Distribution in the Brain and Its Relationship to Depression ................................... 421 20.2.2 Role in Stress and Anxiety .......................................................................................424
