360 3. .V-ETHYLMALEIMIDE 



three are quite markedly reduced by incubation with iV-ethylmaleimide 

 (see accompanying tabulation). Lipoate is reduced only by concentrations 



above 1 n\M .V-ethylmaleimide so it can perhaps be eliminated as a factor 

 in the secretory inhibition. Addition of glutathione does not modify the 

 inhibition and it was believed that this is evidence for discounting the im- 

 portance of glutathione, but possibly the glutathione reacted is tightly 

 bound to some enzyme or transport system and cannot be easily replaced. 

 Slight recovery occurs when coenzyme A is added to inhibited stomachs 

 but only at the lowest iV-ethylmaleimide concentrations, and the results 

 were not considered sufficiently significant to be indicative of the partici- 

 pation of coenzyme A. However, the reduction in coenzyme A and the 

 secretory inhibition proceed in parallel so that at least part of the inhibi- 

 tion may be related to the inactivation of coenzyme A. It may be noted 

 that iodoacetamide does not reduce coenzyme A parallel to secretory 

 inhibition, substantiating a difference in the sites of action of these in- 

 hibitors. Probenecid inhibits certain renal transports and has been suggested 

 to react with coenzyme A. It was found that probenecid above 0.1 mM 

 inhibits acid secretion and that 0.5 mM iV-ethylmaleimide lowers the pro- 

 benecid threshold by a factor of 80. These results are consistent with an 

 action of A^-ethylmaleimide on coenzyme A. The problems and limitations 

 inherent in such analyses of inhibitor action are well illustrated by this 

 work and the original papers will repay careful reading by those interested 

 in using inhibitors to determine the mechanisms of cellular function. 



Axonal Conduction and Ganglionic Transmission 



H. M. Smith (1958) has shown that A^-ethylmaleimide at 2 mM blocks 

 the conduction in frog sciatic nerves in 21 min, and at 1 mM blocks conduc- 

 tion in the lobster giant axon in 10 min. Conduction blockade occurs long 

 before depolarization of the axons — in the case of the lobster nerve it 

 requires 90 min to depolarize — and this might suggest that A^-ethylma- 

 leimide exerts some action other than depolarization, although the latter 



