Development of rolipram-sensitive, cyclic AMP phosphodiesterase (PDE4) in rat primary neuronal cultures

The development of PDE4 was examined in primary neuronal cultures of rat ce rebral cortex. Three days after culturing, neurons exhibited relatively low PDE4 activity (i.e., rolipram-sensitive PDE activity). It gradually increa sed over time, approximately doubling by day 12. The increase in activity w as accompanied by an increase in the expression of the PDE4A variants, PDE4 A5 and PDE4A1, as well as of the synaptic marker protein synapsin I. There was a strong correlation between the expression of the PDE4A variants with that of synapsin 1, which suggests that as neurons develop and signal trans duction increases there is a regulated increase in PDE4 expression and acti vity. Consistent with this interpretation, it was found that treatment with the sodium channel blocker tetrodotoxin, which inhibits depolarization-ind uced neurotransmitter release, reduced the expression of the PDE4A variants . These data demonstrate the developmental regulation of PDE4 in neurons an d offer a manner by which the association of PDE4 variants with particular signal transduction pathways may be studied in vitro. (C) 2001 Elsevier Sci ence B.V. All rights reserved.