920 7. MERCURIALS 



frequently not be compared. For example, mercurials in diuretic dosage 

 inhibit glucose resorption and p-aminohippurate secretion in man, but have 

 no effect on these transports in the dog; also p-MB is not diuretic in the 

 dog, but increases urine flow in the rat (Cafruny and Palmer, 1961). (2) 

 Animals in different states of water load, ion load, or pH wiU respond dif- 

 ferently to the mercurials. (3) The use of theophylline-containing mercurials 

 has often confused interpretation, since theophylline itself is a diuretic act- 

 ing by a mechanism quite different than the mercurials. Thus Goldstein et 

 al. (1961) found Mercuhydrin (meralluride complexed with theophylline) 

 to produce two phases of diuresis, the first due to the theophylline. Certainly 

 some of the results attributed to the mercurials have had their origin in the 

 theophylline present, and for this reason it is always advisable to use mer- 

 curials complexed with inactive substances if a pure mercurial action is to 

 be investigated. (4) Much of the work on distribution of the mercurials and 

 their actions on enzymes in the kidney has been done with toxic or lethal 

 doses or concentrations. If a mechanism for the normal diuretic effect is to 

 be found, one must use mercurial concentrations which do not deviate ap- 

 preciably from those producing maximal diuresis. (5) Different routes of ad- 

 ministration often lead to different results. We have seen that intravenous 

 injection causes changes in blood flow and glomerular filtration not seen 

 with the usual routes of administration. 



Sites of Action in the Nephron 



Several types of evidence have been used to locate the major sites of 

 mercurial action on renal transport processes; these will be discussed briefly, 

 since they also provide interesting information on the mechanisms involved. 



(A) Inhibition of transport processes located in different regions of the 

 nephron. The mercurials interfere with the transport of a variety of sub- 

 stances by the proximal segment of the nephron. This includes the resorp- 

 tion of glucose, amino acids, urate, phosphate, bicarbonate, Na+, K+, and 

 Ca++, and the active secretion of p-aminohippurate, iodopyracet (Diodrast), 

 tetraethylammonium ion, phenol red, and various dyes. Izar (1909) noted 

 an increase in urinary urate in dogs given HgClg intravenously, and Dale 

 and Sanderson (1954) demonstrated that urate excretion in man rises rap- 

 idly following administration of mersalyl. However, if oliguria is produced 

 by lethal doses of HgCla, urate excretion is impaired and the tissue concen- 

 tration will rise (Wells, 1916). Mild poisoning by mercurials leads to an 

 aminoaciduria in man (Clarkson and Kench, 1956). There has been dis- 

 agreement with respect to the effects on glucose resorption, and perhaps in 

 man there is little reduction at diuretic doses, but Vander (1963) has shown 

 a very definite inhibition in the dog, A Tm being around — 100 during max- 

 imal diuresis. Mercaptomerin in dogs lowers the bicarbonate threshold of 

 the proximal tubules by 35% without significant effect on the distal tubules 



