EFFECTS ON PERMEABILITY AND ACTIVE TRANSPORT 187 



indicated either partial antagonism or, more usually, none at all. lodoace- 

 tate at 0.2-0.5 mM inhibits the accumulation of phenol red in isolated 

 kidney tubules. Beck and Chambers (1935) found pyruvate to counteract 

 this inhibition partially and lactate to be less effective, but Forster and 

 Taggart (1950) and Jaffee (1954) observed no effect of lactate added be- 

 fore, with, or after iodoacetate (0.5 mM). Similarly Wilbrandt (1940) ob- 

 tained in erythrocytes partial reversal of the iodoacetate inhibition of the 

 Na+-K+ transport (even though iodoacetate was as high as 10 mM), where- 

 as Maizels (1951) found only very slight antagonism. In algae the situation 

 is more complex. The extrusion of Na+ and accumulation of K+ by Ulva 

 lactuca are inhibited by 1 mM iodoacetate in the dark, the K+ loss being 

 greater than the gain in Na+ (Scott and Hay ward, 1954). Pyruvate com- 

 pletely prevents the rise in cell Na+ induced by iodoacetate but only par- 

 tially antagonizes the K+ loss. In Hormosira banksii 0.1 mM iodoacetate 

 leads to an increase in cell Na+ and a progressive decline in respiration; 

 pyruvate does not modify either action (Bergquist, 1958). Iodoacetate at 

 1 mM reduces the K+/Na+ ratio in frog muscle from 5 to 3.4; in the presence 

 of pyruvate the ratio is reduced to 3.9 (Van der Kloot, 1958). This rather 

 weak antagonism led Van der Kloot to conclude that the site of action is 

 mainly the EM pathway, and from work with other inhibitors that energy 

 from either the cycle or glycolysis can be used for Na+ extrusion. However, 

 it would be more reasonable to conclude that iodoacetate is at least affect- 

 ing significantly systems other than the EM pathway. Indeed, all of these 

 studies point to an inability of pyruvate to counteract completely or at all 

 the transport effects of iodoacetate. This should not be interpreted as prov- 

 ing that the principal site of action is not on the EM pathway, but certainly 

 suggests this, especially since penetration of iodoacetate would make likely 

 the penetration of pyruvate and since cycle energy seems to be able to 

 support transport in most instances. 



If a substrate stimulates transport in the uninhibited preparation, it is 

 sometimes difficult to determine if antagonism of inhibition occurs. The 

 accumulation of Br" by barley roots is definitely stimulated by various 

 cycle intermediates, in both the absence and presence of iodoacetate (Table 

 1-32) (Machlis, 1944). The percentage inhibition by iodoacetate is less in 

 the presence of any of these intermediates than in the endogenous control. 

 This could be interpreted as antagonism. However, what is actually shown 

 is that 0.01 mM iodoacetate does not interfere with the transport-promot- 

 ing activities of these substrates, while 0.05 mM iodoacetate definitely de- 

 presses their effects. The data do not prove that the cycle as a whole is 

 unaffected (e.g., pyruvate oxidation might be inhibited) or that the site of 

 action of iodoacetate, even at 0.01 mM, is entirely on the EM pathway. 

 A similar situation is found in the uptake of tyrosine by rat brain, where 

 glucose increases the cell/medium ratio from 2.73 to 4.63 and in the pres- 



