470 



9. INHIBITION IN CELLS AND TISSUES 



may be relatively simple. In this case, perhaps the structural nature of 

 the enzyme grid allows (Aj) to equal (A^) [{kilk_i)], where k^ and k_i 

 are the diffusion constants for the inward and outward directions through 

 the enzyme screen. The enzyme activity would have the effect of reducing 

 the diffusion rate by destroying a certain fraction of agonist molecules; 

 thus ki may be smaller than k_i and (Aj) smaller than (Ag). Inhibition of 

 the enzyme would change k^ but not k_i since it makes no difference if a 



100- 



FiG. 9-8. Effect of the inhibition of the inactivating enzyme on the action of an agonist. 

 The agonist action is given in per cent of the action produced by the external concen- 

 tration. Same conditions as in Fig. 9-7 and in addition K^ = 10-^ mM and K^ = 1 mM. 



molecule diffusing out is inactivated or not. It can be shown that the in- 

 ternal agonist concentration in the presence of the inhibitor is given by: 



[-^ <•-" + '] 



(A,), = (AJ 1-^ (1 -i) +v 

 (A,), = (A,)(l - i) + i{A„) 



(9-18) 

 (9-19) 



When there is no inhibition, (Aj)^ = (Aj), and when inhibition is complete, 

 the external and internal concentrations are the same, or (AJj = (A^). 

 In case the agonist concentration in the uninhibited state is very low so 

 that it is not affecting tissue function significantly (i.e., when the enzyme 

 is effectively inactivating the agonist almost as rapidly as it is formed), 

 the internal concentration during inhibition will be given approximately 

 by (AJ, = t(AJ. 



