[Possible consequences of acetylcholinesterase inhibition in organophosphate poisoning. Discussion continued].
Numerous toxicologists still believe that the only function of acetylcholinesterase (AChE) is to catalyse the hydrolysis of acetylcholine (ACh), and that the toxicity of organophosphorous pesticides (OP) results from their ability to switch this function off. This viewpoint, however, requires revision in the light of the recent findings concerning the AChE structure and function as well as in view of the regulation of the AChE protein synthesis in conditions of stress. There is now no doubt that apart from catalysing the ACh hydrolysis, AChE performs also nonenzymatic functions, trophic (e.g., stimulation of neuritogenesis and remodeling) and neuromodulatory (promotion of long-term functional changes in the central nervous system). Binding to OP does not interfere with its nonenzymatic functions, but it stimulates AChE mRNA transcription and overproduction of the AChE protein. This results in overexpression of nonenzymatic AChE functions. It is likely that this overexpression is responsible for at least some of the persistent alterations in the CNS functions which may develop after an OP exposure.
Gralewicz
Slawomir
S
Z Zakladu Toksykologii i Kancerogenezy, Instytutu Medycyny Pracy im prof. dra med. J. Nofera w Lodzi. gralslaw@imp.lodz.pl
D000110:Acetylcholinesterase / Q000187:drug effects*; D002493:Central Nervous System Diseases / Q000139:chemically induced; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced; D006801:Humans; D007306:Insecticides / Q000506:poisoning*; D009768:Obidoxime Chloride / Q000506:poisoning; D062025:Organophosphate Poisoning
D007306:Insecticides; D009768:Obidoxime Chloride; D000110:Acetylcholinesterase