580 



12. RATES OF INHIBITION 



made. Much excellent work has recently been done on the penetration of 

 drugs into cells and tissues, chiefly using radioactively labeled material, 

 but very little information on the commonly used inhibitors has been re- 

 ported. It is necessary to obtain not only accurate rate data for these in- 

 hibitions, but to accumulate evidence for penetration rates and the operancy 

 or inoperancy of the factors discussed above. 



Illustrative Examples of Cellular Inhibition 



We shall now present some specific results obtained on various types of 

 cellular preparations in order to emphasize a few fundamental principles 

 and to indicate how simple analyses of the data have been carried out in 

 the past. 



0.8 



0.6 



0.4- 



0.2 

 A 



0.2 mM 



0.042mM 



O.OIOmM - 



40 80 120 



TIME (MINUTES) 



Fig 12-24. Inhibition of glycolysis in rat spleen slices by 

 HgCla (From Jowett and Brooks, 1928.) 



(A) The inhihition of glycolysis in rat spleen slices by HgCla- Jowett and 

 Brooks (1928) found that the rate of inhibition varied with HgCla concen- 

 tration in the manner shown in Fig. 12-24. It is obvious that the curves 

 do not all start from the origin and that a short lag period is present, but 

 since no observations were made in less than 25 min. the course of the 

 curves in this region cannot be recorded. This was the first demonstration 

 of an exponential effect of an enzyme inhibitor in which some attempt to 

 analyze the data kinetically w^as undertaken. They fitted the data to the 

 simple generalized expression: 



V = f'^e-"' (12-86) 



