Inhibition of acetylcholinesterase and butyrylcholinesterase by the organophosphorus insecticide methylparathion in the central nervous system of the golden hamster (Mesocricetus auratus).
The toxic effects of the organophosphorus pesticide methylparathion are primarily caused by the inhibition of acetylcholinesterase activity in the central nervous system, whereas the relationship between butyrylcholinesterase and poisoning symptoms is unclear. The presumed different effects of methylparathion on acetylcholinesterase in various regions of brain and spinal cord suggest differences in the distribution of molecular enzyme forms. In the present work, the in vitro and in vivo effects of methylparathion on acetylcholinesterase and butyrylcholinesterase were studied in whole brain homogenates of golden hamsters with biochemical methods. Furthermore, acetylcholinesterase activity was determined in regions of the nervous system by quantitative histochemistry (microdensitometry). Biochemically, very low IC50 values of the hydrophilic and lipophilic fractions of both enzymes were measured. Analysis of the time course of enzyme inhibition revealed maximum inhibition 45 min after methylparathion application. Using microdensitometry different degrees of acetylcholinesterase inhibition were found in various areas of the brain. The highest inactivation was observed in the Substantia nigra and in thalamic nuclei; in several regions of the cerebellum, the inhibition rate was comparatively lower. In conclusion, methylparathion acts as an potent inhibitor of acetylcholinesterase and butyrylcholinesterase in the hamster nervous system. The region-specific different inactivation of acetylcholinesterase might be caused by the existence of multiple forms of the enzyme in various brain regions.
Hahn
T
T
Section of Biosciences, University of Leipzig, FRG.
Ruhnke
M
M
Luppa
H
H
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D008297:Male; D008647:Mesocricetus; D008743:Methyl Parathion / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D008743:Methyl Parathion; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase