EFFECTS ON TISSUE FUNCTIONS 



359 



sion, but if acetoacetate is used as a substrate instead of glucose the in- 

 hibition of acid secretion remains (Davenport et al., 1955). When iV-ethyl- 

 maleimide is used in conjunction with 2,4-dinitrophenol in the technique 

 previously described (page 1-504), it was found that the inflection point 

 in the concentration-inhibition curve for the uncoupler is shifted somewhat 

 to the left, i. e., iV-ethylmaleimide augments the action of 2,4-dinitrophenol 

 (about one third the concentration required for minimal inhibition), in- 

 dicating the primary effect of iV-ethylmaleimide to be on some process 



Fig. 3-5. Effect of xV-ethylmaleimide on acid se- 

 cretion from mouse gastric mucosa after 10-min 

 exposure. (From Davenport et al., 1955.) 



of ATP formation rather than on ATP utilization. If mouse stomachs are 

 incubated for 10 min with 1 vaM iV-ethylmaleimide, acid secretion is re- 

 duced 80%, and simultaneously there is a 33% inhibition of succinate 

 oxidase (Davenport et al., 1956). However, it was felt that this is not an 

 important site of action and is not the cause of the secretory inhibition. 

 Nevertheless, it may well indicate an appreciable inhibition of the operation 

 of the cycle, inasmuch as succinate oxidase may not be as sensitive to the 

 inhibitor as the «-keto acid oxidases, and this could contribute to the 

 interference with ATP generation. Davenport believed that the SH groups 

 important for acid secretion are not involved in oxidative systems, but 

 rather are on some specific portion of the secretory system. The evidence 

 for this comes mainly from w^ork on iodoacetamide, but there is some 

 doubt if A^-ethylmaleimide acts in exactly the same way since the effects 

 on the susceptibility to 2,4-dinitrophenol are quite opposite. An attempt 

 was made to determine if the critical SH groups are those of glutathione, 

 coenzyme A, or lipoate, and it was found that the concentrations of all 



