OKADAIC ACID AND CULTURED FROG SCIATIC-NERVES - POTENT INHIBITION OF AXONAL REGENERATION IN SPITE OF UNAFFECTED SCHWANN-CELL PROLIFERATION AND GANGLIONIC PROTEIN-SYNTHESIS

Okadaic acid (OA) is a frequently used phosphatase inhibitor that by i nhibiting dephosphorylation increases the net phosphorylation level in various systems. In the present study OA was used to assess the role of balanced phosphorylation-dephosphorylation reactions for successful regeneration of peripheral nerves. To achieve this, the effects of OA on phosphorylation levels, neurite outgrowth, injury-induced support cell proliferation, and neurofilament stability, respectively, were in vestigated in the in vitro regenerating, adult frog sciatic sensory ne rve. OA at a moderate concentration (20 nM) increased phosphorylation levels and almost completely inhibited the in vitro regeneration in a reversible way. The effect on regeneration was not due to induced neur ofilament instability and was only seen when the drug was applied in t he outgrowth region. The latter and the absence of effects on support cell proliferation indicate that OA acts locally at the level of newly formed axons. However, the inhibition of regeneration was not a conse quence of reduced delivery of proteins by axonal transport, because th is process in fact was increased by OA. Altogether, the study suggests that properly balanced phosphorylating-dephosphorylating reactions ar e critical for regeneration of peripheral nerves.