Noncholinesterase effects induced by organophosphate pesticides and their relationship to cognitive processes: implication for the action of acylpeptide hydrolase.
Organophosphate pesticides have been classically described as inhibitors of acetylcholinesterase (AChE) activity in insects and invertebrates. However, there is now more evidence supporting the hypothesis that these compounds also act through noncholinergic pathways, especially those related to cognitive processes. The enzyme acylpeptide hydrolase was identified as a new target for organophosphate pesticides. This enzyme is more sensitive than AChE to some organophosphates (OP), including dichlorvos, which is the parent compound for metrifonate, a therapeutic agent used in the treatment of cognitive impairment associated to Alzheimer's disease. Therefore, there is some doubt as to whether the mechanism of action of this drug is mediated by a potentiation of cholinergic transmission. However, the direct action of acylpeptide hydrolase in cognitive processes and the physiological and molecular mechanisms underlying subacute exposure to OP have yet to be demonstrated. This review deals with evidence demonstrating the existence of mechanisms of actions of OP, which are independent of cholinergic pathway potentiation and which have an effect on cognitive processes. In addition, the possible participation of the enzyme acylpeptide hydrolase in these processes is also discussed. Finally, the possibility of using this enzyme activity as a new biomarker for exposure to OP is considered.
Laboratory of Environmental Neurotoxicology, Department of Biological Sciences, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile. pancetti@ucn.cl
Floria
F
Pancetti
Cristina
C
Olmos
Alexies
A
Dagnino-Subiabre
Carlos
C
Rozas
Bernardo
B
Morales
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002802:Cholinesterases / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D004781:Environmental Exposure / Q000032:analysis; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects; D010755:Organophosphates / Q000633:toxicity*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010575:Pesticides / Q000633:toxicity*; D011480:Protease Inhibitors / Q000633:toxicity*
D015415:Biomarkers; D010755:Organophosphates; D010575:Pesticides; D011480:Protease Inhibitors; D002802:Cholinesterases; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase