EFFECTS ON TISSUE FUNCTIONS 625 



(Weeks et al., 1950). When the intestine is allowed to contract for 30-60 min 

 in the absence of substrate the amplitude is reduced to 15-35% of normal. 

 The addition of glucose, acetate, or pyruvate allows recovery, essentially 

 complete in the case of glucose. Dehydroacetate at 10 mM effectively pre- 

 vents this recovery with acetate and pyruvate, but only partially counter- 

 acts the effect of glucose. This was taken to mean that dehydroacetate blocks 

 the cycle preferentially. Malonate neither depresses the amplitude in the 

 presence of substrates, nor prevents the recovery of substrate-depleted in- 

 testine upon addition of substrates. This could be related to the poor pen- 

 etration of malonate into the cells. Dehydroacetate, even though it may 

 have a double negative charge, might penetrate better than malonate be- 

 cause the lipophilic fraction of the molecule is greater (sodium dehydroace- 

 tate is fairly soluble in a number of organic solvents). 



Heart 



Dehydroacetate given intravenously to dogs causes some slowing of the heart 

 rate at a dose of 300 mg/kg (Seevers et al, 1950), but in general the effects on 

 the cardiovascular system are minimal. Like many substances with the 

 — CH = CH — CO — grouping, dehydroacetate exerts a positive inotropic ac- 

 tion on hypodynamic cat papillary (Bennett et al., 1958). Although not so 

 potent as many other compounds, it is active at 5 mM and rated the same 

 as /3-angelicalactone. Isolated rat atria are depressed quite markedly by 

 5-10 mM dehydroacetate, and to some extent even by 1 mM, and this is 

 accompanied by rather unique effects on the membrane potentials (Webb 

 and Hollander, 1959). The resting and action potential magnitudes are re- 

 duced more strikingly than with most metabolic inhibitors. However, the 

 action potential duration is actually increased, due to a slowing of repolar- 

 ization, an effect observed with no other inhibitor. The depolarization rate 

 is unaffected, so that the moderate slowing of conduction noted must be 

 related to the reduced action potential. Malonate at higher concentration 

 scarcely alters the properties of such atria, again indicating a difference 

 either in penetration or in action. 



Renal Transport 



When dehydroacetate is injected into dogs in amounts sufficient to give 

 plasma concentrations of 20-25 mg% (1.2-1.5 mM), the renal tubular trans- 

 port of certain substances is markedly depressed — p-aminohippurate 81%, 

 phenolsulfonphthalein 80%, penicillin-G 60%, and iV-methylnicotinamide 

 77%, while the transport of glucose, creatinine, and phosphate is unaltered 

 (Shideman et al., 1950 b). Since diuresis is observed after dehydroacetate, 

 it is likely that water and ion transport is also affected to some extent. It 

 is thus clear that certain transport systems are inhibited and others are 



