Biophysical Factors in Drug Action 31 



branes of the component cells. Using appropriate substrates, 

 analogous results can be demonstrated with the phenoloxidase 

 systems, catechol oxidase and tyrosinase, which are also present 

 in the cuticle and internal tissues. 



These results can be most logically explained by postulating 

 a lipoprotein mosaic structure in the cell membranes of the 

 tissues, in which the availabilities of the enzvmes are influenced 

 by the labile lipids present in the structural frameworks. Sim- 

 ilar increases in the availability of these enzymes can be 

 induced in the intact insect by two different kinds of physical 

 stimuli : ( 1 ) heat, which increases cuticle permeability and 

 phenoloxidase activity in the internal tissues, and (2) mechani- 

 cal damage of the cuticle and tissues which exposes the available 

 enzymes. If the posterior segments of an insect such as meal- 

 worm larvae, Tenebrio molitor, are subjected to the action of 

 {a) chloroform, {h) heat (40-45° C), and (c) mechanical dam- 

 age by squeezing, the insects first become paralyzed, and this 

 stage is followed by a similar local blackening in the posterior 

 segments owing to an increase in the availability of tissue 

 tyrosinase in these regions, a change which is associated with 

 an increase in oxygen uptake. 



These results are in accord with Henderson^s suggestion that 

 narcosis and oxidative processes are separable phenomena.^'' 

 Although fat-solvent narcotics appear to exert a physical action 

 on the cell lipids, the secondary changes which cause a disturb- 

 ance in oxidative metabolism may be much more complex. In 

 insects, the increase in tissue-phenoloxidase activity results in 

 the accumulation of reactive o-quinones in the blood and tissues. 

 Richter ^"^ has shown that these oxidation products act as power- 

 ful inhibitors of catechol-oxidase activity ; it is likely that they 

 would exert a general toxic action on the vital processes within 

 the insect. 



Conclusions 



It is doubtful whether this selective environmental influence 

 of the structural tissue components on enzymic activity can be 

 simulated specifically in reconstructed enzyme systems, where 



