538 ANNALS NEW YORK ACADEMY OF SCIENCES 



of about 50 rabbits was injected with 0.3 mg. DFP per kg., and blood 

 samples were taken, before injection, for determination of normal 

 plasma and red cell cholinesterase. At this dose, the rabbits developed 

 tremors within about 15 minutes after injection and continued to have 

 these tremors throughout the day. About 10 per cent of the animals 

 died. The survivijig animals were free of symptoms the day following 

 injection. At suitable intervals after injection, blood was taken for de- 

 termination of plasma and red cell cholinesterase activities. At these 

 or other times after injection, 1 to 6 rabbits were selected for sacrifice. 

 Brains were removed, within 5 minutes after death, and the brain 

 cholinesterase activities determined. The plasma cholinesterase ac- 

 tivity returned to normal values in about 5 days. The red cell cholin- 

 esterase activity returned to normal somewhat more slowly. It was 

 about 50 per cent of normal in about 5 days and attained the normal, 

 pre-injection level in 10 days. The rate of recovery of brain cholin- 

 esterase activity was exceedingly slow. Ten days after injection, the 

 brain cholinesterase activity was about 50 to 60 per cent of normal. 

 Twenty to thirty days after injection, it was about 60 to 70 per cent 

 of normal. Fifty days after injection, the brain cholinesterase activity 

 had returned to 90 per cent of normal. 



Attempts at Reversal of DFP Inhibition of Cholinesterase. It has 

 been shown that the inhibitions of phosphatase by amino acids,^^ of 

 pepsin by proteolytic digestion products,^'' and of cholinesterase by 

 physostigmine^^' ^^ may be reversed by subjecting the enzyme-inhibitor 

 mixture to dialysis or dilution. In the present study, the serum and 

 brain extracts of rabbits injected with 0.3 mg./kg. DFP were dialyzed 

 against several changes of saline, for about 24 hours. Rabbit plasma 

 was also treated in vitro with DFP and then dialyzed, for 24 hours. 

 In neither type of experiment was there any increase in activity of the 

 inactivated cholinesterase. The in vitro results are in agreement with 

 those of Mackworth.^^ Dilution of mixtures of cholinesterase and 

 fluorophosphate failed to show any relative increase in enzyme activ- 

 ity. This was in contrast to the results obtained on dilution of physo- 

 stigmine-cholinesterase mixtures. 



In view of the difference among the cholinesterases of different tis- 

 sues to inhibition by DFP, it would be unjustified to draw any conclu- 

 sions from our data concerning the sensitivity to inhibition of cholin- 

 esterases, at autonomic effector organs, ganglia, or myoneural junctions. 

 According to the concept of chemical transmission of nervous impulses, 

 the extent of cholinesterase inhibition, at these sites, should be corre- 



