934 



7. MERCURIALS 



of the plasma (pH 7.4 to 7.14), does not alter urinary pH significantly, as 

 does administration of NH4CI; no one knows what happens to intracellular 

 pH in the tubules. It may also be pointed out that alkalinization of the 

 urine with acetazolamide or K+ does not alter the diuretic response to mer- 

 curials (Pitts, 1958). 



It is not immediately apparent why Hg++ must be formed from organic 

 mercurials to inhibit renal transport, since in most cases the organic mer- 

 curials react readily with SH groups which may be involved. If mercaptides 

 or dimercaptides participate in the splitting of the mercurials, the Hg++ 

 formed must dissociate from these SH groups and attach to others, because 

 the cell component originally binding the mercurial must be blocked and 

 there would be no necessity for splitting. If Hg++ is necessary for diuresis, 

 it must be that either (1) a cyclic mercaptide is required, or (2) the impor- 

 tant SH groups are not sterically accessible to the larger organic mercur- 

 ials. Weiner et al. (1962) assume that the specific receptor for the diuretic 

 action contains two groups, one being an SH group and the other either an 

 SH group or some other ligand complexing with Hg++ (e.g., an amino 

 group). The complete scheme as outlined by Weiner et al. (1962) is shown 



NONSPECIFIC 

 PROTEIN 



R-Hg-S-PROTEIN 



4= 



R-Hg-S-CYST ■ 



CYST-S-Hg-S-CYSTj 



R-Hg-S-CYST 

 iCYST-S-Hg-S-CYST 



SPECIFIC 

 RECEPTOR 



Fig. 7-45. Scheme of mercurial re- 

 actions in the kidney. (From Weiner 

 et al., 1962.) 



in Fig. 7-45. It is strange that this transport component would not be inhib- 

 ited by organic mercurials bound to one SH group, or that certain potent 

 SH reagents, such as MM or p-MB, would not inactivate it. The nondiuretic 

 p-MB prevents and reverses the diuretic effects of the mercurials, while 

 MM does not do this (Miller and Farah, 1962 a). A competition between 

 p-MB and Hg++ for the receptor SH groups was suggested. Miller and Farah 



