EFFECTS ON PERMEABILITY AND ACTIVE TRANSPORT 907 



was characterized by a lag period, this being due to the preferential binding 

 to SH groups before the imidazole groups are attacked; however, there are 

 other possible reasons for such a lag period, and indeed Wilbrandt (1941) 

 claimed the inhibition occurs before the mercurial is bound intracellularly. 

 They also point out that Cu++ is much more potent than p-MB in depressing 

 glycerol entry and that this favors an imidazole group; p-MB is, however, 

 rather ineffective relative to Hg++, which exerts an effect at 0.025 mM, due 

 possibly to steric factors. It does not appear that the evidence is sufficient 

 to establish an imidazole group as involved in the glycerol transport, but 

 one cannot argue against this theory, and it is quite possible that in the 

 complex mechanisms of penetration there are both SH and imidazole groups. 

 In either case, one cannot attribute an active role to these groups in the 

 transport on the basis of the evidence available. 



EFFECTS ON PERMEABILITY AND ACTIVE TRANSPORT 



The general discussion of the mechanisms by which transport systems 

 in the membrane may be affected by SH reagents (see III-1-171, 180) is 

 applicable to the mercurials. We shall confine our attention to certain 

 important problems and interesting results, as far as possible, and only 

 summarize most of the studies in Table 7-18. The effects of the mer- 

 curials on renal transport wiU be taken up in the following section. It 

 is clear from the results in the table that the mercurials often cause a loss 

 of intracellular substances, e.g., K+, carbohydrate, and amino acids. It is 

 likely that a good many substances leak out of cells treated with the mer- 

 curials as a result of not only interference with active transport but direct 

 distorting effects on the membrane structure leading to increases in per- 

 meability. Possibly coenzymes, enzymes, and other large molecules may be 

 lost. Ohr (1960) observed the release of some ultraviolet-absorbing material 

 from diaphragm exposed to Hg++, and Weed et al. (1962) detected the early 

 release of some Hg++-complexing material from human erythrocytes, this 

 altering the binding kinetics at low concentrations of Hg++. It is not easy 

 to determine if the action is primarily on active uptake or on outward dif- 

 fusion, even with labeled substances. For example, if one is studying K^^ 

 efflux, an inhibition of a pump involved in maintaining a high intracellular 

 K+ level might alter this efflux, either by changing the membrane potential 

 or directly if part of the K+ efflux is mediated by the pump, since a Na+ 

 pump might not be completely specific for Na+ and might carry some K+ 

 out of the cell. If K*^ influx is measured, an alteration of the permeability 

 could easily change the rate at which active transport occurs, particularly 

 if K+ loss accelerates the pump. In most cases there seems to be a decrease 

 in the intracellular K+/Na+ ratio, but the mechanism is not clear. Further- 

 more, a decrease in transport is occasionally not accompanied by a signifi- 



