REVERSAL IN CELLS AND WHOLE ANIMALS 



645 



developed rapidly, indicating rapid penetration into the cells, may not 

 show nearly as fast a reversal of the inhibition when removed from the 

 extracellular medium. Some of the metal chelators, such as 1,10-phenan- 

 throline or 2,2'-dipyridine, may behave in this manner (Webb et al., 1958) 

 and in these instances the limitation of the rate of reversal may be attrib- 

 uted to the rather slow dissociation of these chelators from metal sites 

 in the cells. 



Examples in which the recovery of enzyme activity is dependent on the 

 svnthesis of new enzyme by the tissues are provided by the organophos- 



TIME (DAYS)- 



10 



20 



25 



Fig. 13-15. The recovery of monoamine oxidase activity in mouse brain following 



a single dose of ^-phenylethylhydrazine (32 mg/kg intraperitoneally). The fall in the 



initially elevated brain serotonin is also shown. (From Chessin et al.. 19.59.) 



phorus inhibitors of cholinesterase and the irreversible inactivators of 

 monoamine oxidase. In these cases it requires many days for restoration of 

 normal enzyme activity. The return of monoamine oxidase in mouse brain 

 after a single dose of /?-phenylethylhydrazine is shown in Fig. 13-15. Cor- 

 related with this rise in enzyme activity is the drop in the initially elevated 

 brain serotonin level, which in turn is probably correlated with the return 

 of normal central nervous system function. Single injections of diisopropyl- 

 fluorophosphate similarly inactivate cholinesterase and modify nervous, 



