BODANSKY: CHOLINESTERASE 539 



lated with the appearance of various chohnergic symptoms. In gen- 

 eral, in the monkey or rabbit, such cholinergic symptoms as muscular 

 tremors, salivation, and diarrhea were associated with low red cell and 

 brain cholinesterase activity, and death was associated with zero brain 

 cholinesterase activity. However, this association is to be regarded as 

 fortuitous. Conversely, it should be emphasized that depression of 

 serum cholinesterase activity does not necessarily indicate the appear- 

 ance of cholinergic symptoms. In monkey and man, for example, the 

 sei'um cholinesterase activity may be reduced to extremely low levels, 

 without the manifestations of such symptoms. 



The persistence of low serum, red cell, and brain cholinesterase ac- 

 tivity in the rabbit, for periods of 5, 10, and 60 days, respectively, and 

 of low serum cholinesterase activities in the monkey and man, for 

 periods of at least one to two weeks, offers evidence in support of the 

 irreversibility of inactivation in vivo. Hall and Ettinger'*° found that, 

 after injections of physostigmine in the dog, the serum cholinesterase 

 activity dropped to 10 to 25 per cent of normal in about a half hour 

 and returned to normal in two hours. This prompt restoration of nor- 

 mal activity may well be expected in the case of a readily reversible 

 inhibitor-enzyme complex. On the other hand, the long periods of 

 time necessary for the restoration of normal cholinesterase activity, 

 after exposure to DFP vapor or injections with DFP solutions, in the 

 instances mentioned, are of the same order of magnitude as those nec- 

 essary for the regeneration of protein/^ and would seem to indicate a 

 synthesis of enzyme protein. 



DFP has already been proved to be of considerable value as a tool in 

 investigative work. Its anticholinesterase action has made it a candi- 

 date for clinical trials in Myasthenia gravis and glaucoma.*^"^'' The 

 marked degree to which it may inhibit cholinesterase activity in vivo, 

 and the character of this inhibition, have, as we have seen, permitted 

 studies of the rate of regeneration of various tissue cholinesterases. 

 They open the way to further studies on the way in which diet, drugs, 

 or the existence of various pathological lesions influence the regenera- 

 tion of cholinesterase. We have also seen that DFP has permitted 

 more incisive studies into the role of cholinesterase in nerve transmis- 

 sion."' '^^ 



SPECIFICITY 



Specificity of Cholinesterase Action. The question of the specificity 

 of the cholinesterase activities of various tissue extracts has claimed 

 considerable attention. Although certain general distinctions between 



