EFFECTS ON THE KIDNEY 923 



some time after maximal urine flow. Renal damage and conversion of SH 

 to S — S groups could be related in some as yet unexplained way. 



These results all demonstrate that mercurials react with renal SH groups, 

 and that some selectivity on certain regions may be exerted, but do not 

 necessarily have any bearing on the site of transport inhibition, since the 

 SH groups involved in the transport (assuming they are) may be only a 

 very small fraction of the total in the tissue; indeed, it is quite possible that 

 only 1-2% of the total SH groups need be reacted to produce maximal 

 diuresis. 



(C) Reduction of electrical potentials of tubular cells. There are two elec- 

 trical potentials of the proximal tubular cells of the isolated Necturus neph- 

 ron, a transmembrane potential of —72 mv and a transtubular potential 

 of —20 mv (lumen negative) (Giebisch, 1958, 1960, 1961). Chlormerodrin 

 in a concentration around 220 //g Hg/g tissue reduces both potentials; in 

 the perfused nephrons the transmembrane potential is decreased 62% and 

 the transtubular potential 63%. Since these potentials are dependent on 

 active ion transports, quite possibly they relate to renal function. These 

 results show that mercurials can affect the proximal tubules, but whether 

 this is related to the diuretic effect is impossible to say. 



(D) Pattern of accumulation of mercurials in the kidney. The kidneys of 

 rats poisoned with HgClj (3 mg/kg intraperitoneally) were examined from 

 5 min to 48 hr afterward by the silver sulfide method, and mercury was 

 found to be deposited first in the endothelial cells of the interstitial capilla- 

 ries, then in the glomerular tufts, and eventually in the epithelium of the 

 proximal tubules, beginning apically and progressing toward the bases of 

 the cells (Wockel et al., 1961). The mercury in the proximal ceUs is partic- 

 ularly associated with the basally situated mitochondria. It was conclud- 

 ed that Hg++ is filtered through the glomerulus and picked up by the tu- 

 bular cells during resorption, which is the most obvious route for Hg++ 

 and one which explains the early and marked effects on the proximal tu- 

 bule. However, it has recently been claimed that another route is more 

 important. Brun et al. (1947) suggested that mersalyl is secreted by the tu- 

 bular cells, and that this accounts for the high concentration of mercury in 

 the tubules and the selective effects on proximal transport. It was claimed 

 by Borghgraef et al. (1956) that the excretory rate of chlormerodrin is 

 too fast for glomerular filtration, especially considering that a large frac- 

 tion of the plasma mercurial is bound and not filtered, and that tubular 

 secretion is responsible for essentially all the mercury in the tubules. This 

 theory has also been proposed by Weiner et al. (1956), Kessler et al. (1957 

 a, b), and Campbell (1959). Greif (1960) held that the uptake of Hg^o^ 

 by Phascolosoma nephridia is an active transport, presumably because it is 

 inhibited by cyanide; however, no inhibition by '2,4-dinitrophenol, azide, 

 or iodoacetate was noted. Despite the evidence for the tubular secretion of 



