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 neurite outgrowth. Some acetylcholinesterase (AChE) inhibitors can inhibit neurite outgrowth, but it is unclear if this is due to inhibition of AChE. In this study, the effect of cholinesterase inhibitors on neurite outgrowth from chick sympathetic neurons was examined. Very high (micromolar) concentrations of tacrine and BW284c51 were needed to inhibit neurite outgrowth. In contrast, nanomolar concentrations were required to block cholinesterase activity. No correlation was found between the type of inhibitor or potency of cholinesterase inhibition and inhibition of neurite outgrowth. Both tacrine and BW284c51 were neurotoxic at concentrations that inhibited outgrowth. Therefore, the action of cholinesterase inhibitors on neurite outgrowth may be due to non-specific toxicity rather than to cholinesterase binding.
Postuma
R B
RB
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
Sáez-Valero
J
J
Small
D H
DH
D000818:Animals; D002642:Chick Embryo; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology; D009474:Neurons / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000201:enzymology
D002800:Cholinesterase Inhibitors; D002802:Cholinesterases