EFFECTS ON THE KIDNEY 927 



phosphatase, or glucose-6-phosphatase (Shore et al., 1959; Bickers et al., 

 1960), but toxic doses lead to a diffuse distribution of various phosphatass 

 in the tubular cells, and some inactivation (Wachstein and Meisel, 1957). 

 Very little work has been done on ATPase, but there is shght evidence that 

 it can be inhibited in the kidney by both mersalyl (DeGroot et al., 1955) 

 and p-MB (Padykula and Herman, 1955). It is probably fair to say that 

 none of these investigations of phosphatases has established a relation to 

 their role in transport or mercurial diuresis. 



Effects on Renal Metabolism 



Mercurials can certainly depress the respiration of kidney at fiufficiently 

 high doses, and this may possibly be a factor in the renal damage produced, 

 but there is little evidence that nontoxic diuretic doses of the mercurials 

 reduce Og consumption. The early work of Gremels (1929) indeed showed 

 that, in the heart-lung-kidney preparation, mersalyl actuaUy increases renal 

 respiration during diuresis. Cohen (1953 a,b) showed particularly well the 

 difference between diuretic and toxic doses. Mercaptomerin at a dosage of 

 10.7 mg Hg/kg in rats produces a marked diuresis. After 1 hr the animals 

 were sacrificed and a mitochondrial suspension prepared from the kidneys; 

 no change in the Og uptake was noted, and the P : ratio may actually 

 have been increased. However, with a toxic dose of 26.7 mg Hg/kg, the O2 

 uptake was depressed 35% and the P:0 ratio dropped from 0.55 to 0.092. 

 Very similar effects were observed on kidney slices, only toxic doses reduc- 

 ing the respiration. Even toxic doses do not affect the O2 uptake or P:0 

 ratio of liver mitochondria obtained from poisoned animals. That mercurials 

 exert very little effect on the cycle when given in diuretic doses was demon- 

 strated by Fawaz and Fawaz (1954). Rats were poisoned with fluoroacetate, 

 and citrate accumulation was determined in the heart and kidney of control 

 animals and those given mersalyl at 4-5 mg Hg/kg; no significant change 

 in citrate formed was noted, so that the operation of the cycle would seem 

 to be unaltered. Although these results indicate no appreciable interference 

 with coenzyme A, Leuschner et al. (1957) claimed that the coenzyme A 

 induced acetylation of sulfanilamide is reduced by HgCla, mersalyl, and 

 mercaptomerin in the same order of potency as for diuresis. Toxic doses 

 reduce the coenzyme A reaction, but it is not certain if diuretic doses are 

 able to do this. The mercurial diuresis is less in coenzyme A-deficient rats, 

 but the significance of this is unknown. Eesults on oxidative phosphoryla- 

 tion are contradictory. Greif and Jacobs (1958) found that even large doses 

 of chlormerodrin (up to 20 mg Hg/kg, which is 20 times the diuretic dose) 

 do not alter the P : ratio of kidney mitochondria with glutamate as the 

 substrate, but Shore and Shore (1960) reported a marked fall in P:0 ratio 

 with a-ketoglutarate as the substrate following toxic doses (3 mg Hg/kg) 

 of HgCl^. 



