Evidence for the activity of five adenosine-3',5'-monophosphate-degrading phosphodiesterase isozymes in the adult rat neocortex.

In the present study, the expression of the activity of adenosine-3',5'-monophosphate-degrading phosphodiesterases (cAMP-PDEs) was analyzed in rat neocortex homogenates. Following separation by anion-exchange chromatography, the isozymes were characterized by their sensitivity to modulators and by their kinetic properties. We identified the activity of five distinct cAMP-PDE isozymes: two calcium/calmodulin-dependent forms (PDE 1), one PDE 2 isozyme stimulated by guanosine-3',5'-monophosphate (cGMP), one cGMP-inhibited form (PDE 3) and a cAMP-specific, rolipram-sensitive form (PDE 4). Our study provides, for the first time, evidence for the existence of PDE 3 enzyme activity in rat neocortex and predicts the expression of at least two isoforms (splice variants) of PDE 1A in this brain area. The existence of different cAMP-degrading phosphodiesterases modulated by different intracellular second messengers (calcium and cGMP) suggests that the activity of neocortical neurons and glia cells is regulated, inter alia, by a 'crosstalk' between calcium-, cGMP- and cAMP-dependent second messenger pathways.