Inhibition of neurite outgrowth from chick sympathetic neurons by cholinesterase inhibitors is not mediated by binding to cholinesterases

Several studies have suggested a role for cholinesterases in regulating neu rite outgrowth. Some acetylcholinesterase (AChE) inhibitors can inhibit ne urite outgrowth, but it is unclear if this is due to inhibition of AChE. In this study, the effect of cholinesterase inhibitors on neurite outgrowth f rom chick sympathetic neurons was examined. Very high (micromolar) concentr ations of tacrine and BW284c51 were needed to inhibit neurite outgrowth. In contrast, nanomolar concentrations were required to block cholinesterase a ctivity. No correlation was found between the type of inhibitor or potency of cholinesterase inhibition and inhibition of neurite outgrowth. Both tacr ine and BW 284c51 were neurotoxic at concentrations that inhibited outgrowt h. Therefore, the action of cholinesterase inhibitors on neurite outgrowth may be due to non-specific toxicity rather than to cholinesterase binding. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.