ACTION ON CELLULAR AND TISSUE METABOLISM 



503 



acetate into the cycle; yet if oxygen uptake were being measured, no 

 antagonism would be observed. 



Renal excretion of an inhibitor makes it possible for a second inhibitor 

 to alter the rate of disappearance from the organism. If the inhibitor is 

 either actively secreted or resorbed by the tubular cells, block of these 

 transport mechanisms would prolong or reduce the stay of the inhibitor 

 in the body. If the inhibitor is passively resorbed with the tubular fluid, 

 a second inhibitor, such as a mercurial, would increase the excretion rate 

 somewhat. 



I 5 



CITRATE 

 (rr.g /gram] 



Fluoroace'tate 



Fluoroacetate after malonate 



riMECHours) ' 



Fig. 10.5. Accumulation of citrate in the thymus follo- 

 wing administration of fluoroacetate alone and fluoro- 

 acetate after malonate. (From Potter et al., 1954). 



It is well known that many inhibitors can change the permeability prop- 

 erties of cells, presumably by modifying the metabolism upon which the 

 structure and function of the membrane depend. It is thus likely that the 

 ability of an inhibitor to penetrate into cells or tissues can be changed in 

 the presence of another inhibitor. An increase in the permeability would 

 particularly aifect the response to those inhibitors which normally expe- 

 rience some difficulty in entering cells. The pattern of distribution of an 

 inhibitor in the various tissues of an animal could well be altered by the 

 prior administration of another inhibitor. 



