948 7. MERCURIALS 



Ruskin and Ruskin (1953), where 5.8 mM meralluride depresses rat heart 

 slices 57%, are scarcely pertinent to understanding how the mercurials act. 

 We have postulated previously that the site of mercurial action on the heart 

 is mainly at the membrane to alter ionic fluxes. This does not imply that 

 the action is nonmetabolic, since enzymes in the membrane may be the 

 ultimate vulnerable points of attack. 



Smooth Muscle 



It is necessary to consider briefly the effects of the mercurials on smooth 

 muscle, if only because calomel was used for centuries as a purgative. We 

 have not discussed Hg+ because little is known about its actions on meta- 

 bolic systems. Hg++ salts are also capable of causing diarrhea, and it is 

 likely that Hg+ is active after being oxidized to Hg++. Hand et at. (1943) 

 developed histochemical tests for Hg, Hg+, and Hg++, and found in various 

 animals that within a few minutes of the intravenous injection of mercurous 

 acetate they could detect both Hg+ and Hg++ in the parenchymal and en- 

 dothelial cells of the kidney, the latter predominating. Whole blood oxi- 

 dizes Hg+ to Hg^^ quite rapidly. Many theories of the mechanism of the 

 purgative action, several rather fanciful, have been advanced, but very 

 few justify even serious criticism. HgClg did not achieve its name of "cor- 

 rosive sublimate" in vain; it is a direct irritant of tissues, by which is meant 

 that it induces cellular damage of both metabolic and nonmetabolic origin, 

 this initiating an inflammatory sequence, which in the intestine causes in- 

 creased activity, depression of the ability to absorb water and various sub- 

 stances, and consequently colitis and diarrhea. In severe mercury poison- 

 ing there is a hyperemic and hemorrhagic appearance of the intestine, with 

 erosion and necrosis. One is thus tempted to attribute the diarrhea to such 

 a nonspecific action, but there is some evidence against this. Isolated in- 

 testine is stimulated in a characteristic way by Hg++ in low concentrations 

 (0.004-0.02 mM), tonic contractions being markedly increased with sup- 

 pression of rhythmic activity (Salant and Brodman, 1929 b). Organic mer- 

 curials apparently can stimulate similarly; e.g., merbaphen augments peri- 

 staltic activity of isolated cat intestine (Govorov, 1936), and p-MB at 

 0.0057 mM stimulates the rat intestine around 10% (Goodman and Hiatt, 

 1964), although p-MB was reported to inhibit rabbit intestine (Haley, 1945), 

 perhaps because of too high a concentration (not given, but around 0.02 

 mM). The stimulations produced by both Hg++ and merbaphen are readily 

 blocked by atropine, indicating that the action is to some extent mediated 

 through the vagal nerves in the intestine. Govorov believed merbaphen to 

 be a parasympathomimetic substance. There is also some increase in the 

 sensitivity of the intestine to vagal stimulation when the tissue is treated 

 with Hg++, recalling similar actions on the heart, and it is possible that 

 inhibition of cholinesterase is involved. However, it seems unlikely that 



