192 1. lODOACETATE AND lODOACETAMIDE 



glucose resorption in perfused frog kidney, iodoacetate given to frogs, rats, 

 and rabbits at a dose of 0.1 g/kg kills the animals before detectable glucosuria 

 occurs {Walker and Hudson, 1937). The transport of ?)-aminohippurate is 

 also readily inhibited by iodoacetate (Fig. II-1-18) (Farah and Rennick, 

 1956); at 0.3 mM the inhibition is 86%, although the respiration is reduced 

 only 30% (Cross and Taggart, 1950), even though 10 mM acetate is present. 

 The effects of iodoacetate on renal ion transport have not been investi- 

 gated in much detail, unfortunately. Rabbit kidney slices, incubated' in 

 0.15 M NaCl to lower the K+ content and then placed in 10 mM K+ me- 

 dium with acetate, reaccumulate K+ and extrude Na+. Iodoacetate at 0.33 

 mM inhibits this almost completely (see accompanying tabulation) (Mudge, 



K+ (meq/kg) Na+ (meq/kg) (?o. 



1951). However, anaerobically iodoacetate at 1 mM has no effect on intra- 

 cellular K+ or the rate of K+ exchange, indicating that K+ transport is 

 not directly related to glycolysis (Mudge, 1953), so that the aerobic inhi- 

 bition is presumably due to a block of pyruvate formation. Different re- 

 gions of the kidney exhibit different patterns of metabolism. The inner 

 zone of the medulla of the dog kidney has a high rate of anaerobic glycoly- 

 sis and a relatively low respiratory rate, and can reaccumulate K+ anaer- 

 obically, whereas the renal cortex cannot (Kean et al., 1961). Iodoacetate 

 at 1.7 mM not only prevents this influx of K+ but causes a further loss of 

 K+ from the inner medulla. However, it is impossible to attribute the inhi- 

 bition to an action on the EM pathway in either rabbit or dog kidney, since 

 the site of action may be the transport system itself, especially in view of 

 the fact that acetate was present aerobically in the work of Mudge, and the 

 concentration of iodoacetate used by Kean et al. is quite high. 



The effects of iodoacetate and iodoacetamide on renal function in intact 

 animals are complex and depend markedly on the concentration of the in- 

 hibitor reaching the kidney. Either decreases or increases in the rate of urine 

 formation may thus be observed. When iodoacetamide is infused into the 

 renal artery of the dog, these differences are very clearly shown (see ac- 

 companying tabulation) (Strickler and Kessler, 1963). The selective effects 

 on certain transport systems are also evident. The results of Herms and 

 Malvin (1963) are different in some respects, although intraarterial infusion 

 into dogs was also the means of introducing the inhibitor. Iodoacetate was 



