EFFECTS ON TISSUE FUNCTIONS 363 



mide 1-20 mM, and this is claimed to be mainly due to an increase in per- 

 meability to K+ (Giebel and Passow, 1961). This may be true at the be- 

 ginning, when K+ loss is faster than Na+ uptake, but later may more likely 

 be attributed to an inhibition of the active accumulation of K+. Jacob and 

 Jandl (1962) found that K+ loss occurs when all the erythrocytic glutathione 

 is reacted and when glycolysis starts to be inhibited, whereas p-MB causes 

 early K+ loss unassociated with metabolic changes and presumably acts 

 directly on the membrane. The ATP required for Na+ — K+ transport is 

 about half contributed from glycolysis, and 1 mM iV-ethylmaleimide 

 depresses this and shifts the source of energy so that, at least under certain 

 conditions, the transport is not immediately affected (Sen and Post, 1964). 

 The EM pathway, however, is not markedly inhibited since there is an 

 elevation of pyruvate which partially compensates for the decrease in 

 lactate. There is thus evidence both for and against the glycolytic inhi- 

 bition being responsible for the loss of K+, but whether this is related to 

 the disappearance of some of the glutathione is not known. 



Miscellaneous Cell Functions 



A^-Ethylmaleimide like several other SH reagents slightly stimulates 

 the motility of the rat intestine, this occurring maximally around 0.0057 

 mM, and blocks the stimulation produced by acetylcholine at 0.57 mM, 

 at which time 76% of the SH groups have been blocked (Goodman and Hiatt 

 1964). Even at 0.001 mM it depresses the acetylcholine response, suggesting 

 that the acetylcholine receptor may contain SH groups. It is not known if 

 A^-ethylmaleimide can release histamine, but at 1 mM it is able to completely 

 abolish the histamine release induced by antigen in sensitized guinea pig 

 lung (Edman et al., 1964). The reaction is not with the antigen or antibody 

 so that some essential tissue component must be inactivated. We have seen 

 that A-ethylmaleimide blocks the uptake of glucose in several tissues and 

 this could play a role in the effects on muscle activity. Diaphragm muscle 

 possesses a transport system for D-xylose and related sugars, and this is 

 inhibited 80% by 1 mM A-ethylmaleimide (Battaglia and Handle, 1959, 

 1960). It was postulated that the carrier contains SH groups with which 

 the sugars may combine, but inhibition by SH reagents could certainly 

 be interpreted in several other ways. The transfer of phosphate across the 

 membranes of staphylococci is an exchange diffusion process involving a 

 carrier. A"-Ethylmaleimide inhibits this exchange at pH 7 and it was con- 

 cluded that the carrier possesses SH groups of rather low reactivity (Mitchell 

 1954). Again, there is no real evidence that the carrier itself contains SH 

 groups. 



The only investigation of A^-ethylmaleimide on the heart gave the sur- 

 prising result that it exerts a positive inotropic action on the cat papil- 

 lary muscle (Bennett et al., 1958). Although several metabolic inhibitors 



