Synthesis of Cholinesterase Following Poisoning with Irreversible Anticholinesterases:Effects of Theophylline and N6, O2-Dibutyryl Adenosine 3',5'-Monophosphate on Synthesis and Survival.

摘要

The half-time for return of whole blood cholinesterase (ChE) activity in mice following Soman and DFP poisoning is 30hours;in rats,following Soman poisoning it is 32hours and 106hours following DFP poisoning. In fact,the recovery of ChE activity in other rat tissues (liver and brain) is also significantly (p<0.001) slower after DFP poisoning than after Soman poisoning. It appears that DFP adversely affects the normal rate for synthesis of ChE only in rats. However, DFP does not affect overall protein synthesis in the rat as measured by C(14)-amino acid incorporation into protein. Pretreatment of mice with a combination of theophylline/dibutyryl cAMP (T-DBcAMP) before poisoning with Soman causes animals to be more sensitive to the poison. Thus,cyclic AMP appears to play a role in antiChE poisoning. Treatment of mice and rats intraperitoneally (ip) with T-DBcAMP at 24,29,and 45hours after Soman poisoning produces a dramatic increase in whole blood ChE but not in brain ChE at 48hours;this increase in enzyme activity is due to pseudo-ChE and not to acetyl-ChE. Ethionine,injected (ip) 1hour before the initial dose of T-DBcAMP,completely abolished the enhanced ChE activity observed in whole blood. These results suggest that the enhanced ChE activity observed in blood is due to a stimulating effect of the drugs on de novo synthesis and/or a release of ChE by the liver. (Author)