212 1. MALONATE 



isolated cat carotid body is lowered by perfusion with malonate (Anichkov, 

 1953). These meager data are all we have to understand the actions of mal- 

 onate on nerve function. Unfortunately, little has been done on junctional 

 transmission, inasmuch as it might be predicted that the synapses would 

 be more sensitive to malonate than are the axons, because of both a higher 

 permeability of such regions to anions and a greater energy requirement 

 for the synthesis of acetylcholine. 



Skeletal and Smooth Muscle Function 



Essentially nothing is known of the effects of malonate on skeletal muscle. 

 Beckmann (1934) claimed that 6.7 mM malonate causes a swelling of muscle, 

 indicating an alteration of permeability. This was termed a membrane- 

 loosening effect. In the initial work of Ling and Gerard (1949) with intra- 

 cellular microelectrodes, it was observed that 10 toM malonate drops the 

 resting potential of frog sartorius muscle from 78 mv to 65.3 mv over a 

 period of 3 hr. This may be correlated with the suppression of Na+ ex- 

 trusion observed by Kernan (1963) in the same muscle, 30% inhibition 

 being produced by 1 mM malonate over 2 hr, an effect similar to that oc- 

 curring in brain slices (Bilodeau and Elliott, 1963). No direct work on the 

 contractile response to malonate has been done. 



The contractions of isolated rabbit intestine are not inhibited by 10 mM 

 malonate, whether in the absence of substrate or in the presence of either 

 acetate or glucose (Weeks and Chenoweth, 1950; Weeks et al., 1950). In- 

 deed, there is a tendency for malonate to increase the contractile activity 

 slightly, especially with glucose as the substrate. There is also no interfer- 

 ence with the recovery of substrate-depleted strips produced by the ad- 

 dition of acetate or pyruvate. It was suggested that a lack of penetration 

 of malonate into the smooth muscle cells might be responsible. Fluoroacetate 

 is quite inhibitory under the same conditions so that some relationship of 

 the contractility to the cycle is likely. The contractile properties of the 

 vascular smooth muscle in the cat hind limb are not affected by 1 mM 

 malonate (Hitchcock, 1946), and the behavior of electrically stimulated pig 

 carotid artery is not altered by 10 mM malonate (Jacobs, 1950). 



It would be important to know more about the possible effects of mal- 

 onate on the formation and release of the neurohormones, such es acetyl- 

 choline and the catecholamines, but the data are not available. It is in- 

 teresting to note, however, that malonate is reasonably effective in inhi- 

 biting the release of histamine from guinea pig lung slices during an ana- 

 phylactic reaction (Moussatche and Prouvost-Danon, 1958). The inhibition 

 is 10% at 20 mM, 40% at 40 mM, and 50% at 60 mM. The inhibition was 

 attributed to the effect on succinate dehydrogenase. Nevertheless, malonate 

 at 40-60 ToM has virtually no effect on the release of histamine brought 

 about by the application of the histamine-releaser Compound 48/80 (Mous- 



