914 7. MERCURIALS 



sue/medium ratio of 5.8, and 1 mM Hg++ reduces this to 1.5 (Schachter 

 et al., 1960). The transport across the intestinal wall leads to an inside- 

 outside ratio of 4.6, and 1 mM Hg++ drops this to 1.1 (Schachter and Rosen, 

 1959). Thus in this instance there is no significant difference in the mercurial 

 inhibition, but certain other inhibitors affect the transintestinal process 

 more strongly. The results wiU often depend on the location of the active 

 transport mechanism. We shall see that this is an important point in con- 

 sidering the effects of the mercurials on the kidney. 



Mitochondrial K+ 



Mitochondria isolated from rat liver in 0.25 M sucrose contain 620-640 

 -//moles K+/g N and this can be lost if the mitochondria are placed in hypo- 

 tonic media or treated with saponin, 2,4-dinitrophenol, or Hg+"'" (Spector, 

 1953). Most of the K+ appears to be free, but a fraction may be bound; the 

 retention of the free K+ is dependent on oxidative phosphorylation. How- 

 ever, Gamble (1957) found that mitochondrial fragments catalyzing oxida- 

 tive phosphorylation can bind K+. This binding is not dependent on ATP 

 but is abolished by 2.4-dinitrophenol, and a relation between the K+ bind- 

 ing and the sites for oxidative phosphorylation was postulated. Hg++ at 

 0.01 mM and p-MB at 0.03 mM produce a 5-fold increase in the K+ ex- 

 change rate. This was later investigated in detail (Scott and Gamble, 1961), 

 and Hg++ in concentrations around 0.01 mM was found to increase the ex- 

 change rate, reduce the bound K+ by 50%, and inhibit phosphorylation 

 50%. The organic mercurials are less effective. These three actions are pre- 

 sumably not mediated through the same mechanism, since EDTA prevents 

 the effects of Hg++ and p-MB on K+ binding, has no effect on the stimulation 

 of the exchange rate, and protects oxidative phosphorylation from Hg++ 

 but not from p-MB. These complex relationships are not completely under- 

 stood at the present time, but obviously are of importance in certain cases 

 of K+ accumulation and transport. 



Gastric Acid Secretion 



Reduction of gastric acidity by 0.25 mM Hg++ introduced into the stom- 

 ach was shown by Mann and Mann (1939), and the mechanisms involved 

 were studied by Davenport and his group at Utah. Gastric secretion of 

 HCl is depressed to a basic level by 1 mM p-MB; if the secretion is stimul- 

 ated by carbachol or histamine, the inhibition appears to be greater but 

 the rate is reduced to the same level (Fig. 7-42), i.e., p-MB effectively abol- 

 ishes the secretion brought about by these drugs (Davenport, 1954, Da- 

 venport et al., 1954). There is thus a basal level of secretion (around 30% 

 of maximal) resistant to the mercurials. Graphical analysis indicated that 

 2 SH groups are involved in the inhibition. Lactate formation when glu- 



