534 ANNALS NEW YORK ACADEMY OF SCIENCES 



showed approximately the same degree of sensitivity toward inhibition 

 by DFP (pCi values of 5.2 to 5.5), whereas human brain cholinesterase 

 (pCi = 6.0) was somewhat more sensitive than monkey or rabbit brain 

 chohnesterase (pCi = 5.5) to inhibition by DFP. Purified cholin- 

 esterase of the electric eel gave a pCi value of 4.1. 



It is of interest to compare the sensitivities of the various tissue 

 cholinesterases from one species to inhibition by DFP. Rabbit brain 

 and red cell cholinesterases showed a greater sensitivity than did serum 

 cholinesterase; brain showed the greatest sensitivity. Thus, a 50 per 

 cent inhibition of serum cholinesterase activity occurred at a negative 

 log of the molar concentration of DFP of 4.1, whereas the same degree 

 of red cell and brain cholinesterase inhibition occurred at values of 5.2 

 and 5.5, respectively. Monkey serum cholinesterase was much more 

 sensitive to inhibition by DFP than red cell or brain cholinesterase. 

 Human serum cholinesterase was much more sensitive to inhibition by 

 DFP than human red cell or brain cholinesterase. This picture is 

 similar to that found in the monkey, and is in marked contrast to that 

 observed in the rabbit. 



Table 6 also shows the sensitivities of rabbit serum, human serum, 

 and muscle cholinesterases to inhibition by physostigmine. It may 

 be seen that rabbit serum cholinesterase was more sensitive to 

 inhibition by physostigmine (pCi = 5.9) than by DFP (pCi = 4.1), 

 whereas the reverse was true with human serum cholinesterase. 



The possibility existed that the differences in sensitivity of different 

 cholinesterases to inhibition by DFP were due to materials, other than 

 the enzymes themselves, present in the preparations. Table 6 shows 

 that a purified horse serum cholinesterase preparation had, within 

 experimental error, the same pCi value as horse serum itself. Heat- 

 inactivated extracts of one tissue, added to a tissue possessing cholin- 

 esterase activity, did not alter the sensitivity of the latter to inhibition 

 by DFP. Thus, human brain extract was heated to destroy its cholin- 

 esterase activity, and added to human serum. The pCi value for the 

 mixture was 7.7, the same as that found for human serum cholinesterase 

 itself. 



In Vivo Inhibition of Cholinesterase Activity by DFP. The extent 

 to which various cholinesterases are inhibited in vivo, after administra- 

 tion of DFP, may be considered to depend, not only on the sensitivity 

 of the particular tissue cholinesterase to inhibition by DFP, but also 

 on the localization and, hence, of the concentration of DFP in the tissue. 

 In rabbits exposed to DFP vapor, severe muscular tremors and death 



