Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate + H(+) 3',5'-cyclic AMP + H2O = AMP + H(+) 3',5'-cyclic GMP + H2O = GMP + H(+) Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. Inhibited by dipyridamole and moderately by IBMX, zaprinast and rolipram. Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1. Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1. Homodimer. Detected in striatum and testis (at protein level). Detected in whole brain, hippocampus, olfactory bulb, striatum neurons and testis. Up-regulated in brain after seizures. Up-regulated in the hippocampus one hour after induction of long-term potentiation. The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity. Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region. Belongs to the cyclic nucleotide phosphodiesterase family.