EFFECTS ON ANIMAL TISSUE FUNCTIONS 723 



EFFECTS ON ANIMAL TISSUE FUNCTIONS 



The injection of o-iodosobenzoate into animals or its application to skeletal 

 muscle preparations does not produce rigor so readily as does iodoacetate. 

 In the whole animal, indeed, the actions on muscle seem to be of little im- 

 portance, and the paralysis sometimes seen is more likely explained by a 

 central effect. Applied directly to isolated frog muscle in reasonably high 

 concentration, o-iodosobenzoate can lead to a loss of excitability and the 

 development of contracture, whereas o-iodobenzoate, although it depresses 

 excitability somewhat, does not induce contracture (Jahn, 1914). The turtle 

 biceps muscle is also slowly and irreversibly shortened by o-iodosobenzoate 

 (and iodoacetamide) at concentrations much higher than would be reached 

 in vivo (Pisanty, 1948). If the mechanism of iodoacetate in contracture is a 

 block of glycolysis, o-iodosobenzoate does not seem to share this selectivity, 

 which confirms what little is known from the results on enzymes and me- 

 tabolism (see page 721). The ability of myosin to associate with actin and 

 to split ATP depends on SH groups and is inhibited by o-iodosobenzoate as 

 well as by other SH reagents (Bailey and Perry, 1947), and the binding of 

 Ca++ by G-actin is depressed parallel to the reduction in polymerization 

 by o-iodosobenzoate (Barany et al., 1962). In these respects, o-iodosoben- 

 zoate is more potent and rapidly acting than iodoacetamide, and such ef- 

 fects may play a role in the contractures observed at high concentration, 

 although a metabolic site of action is not excluded. The contractile response 

 to ATP by nonconducting psoas muscle fibers is abolished by 0.5-1 mM 

 o-iodosobenzoate, and this is reversible if the fibers are incubated for 90- 

 120 min in 10 mM cysteine (Korey, 1950). 



The heart appears to be more sensitive to o-iodosobenzoate than is skele- 

 tal muscle. In the initial pharmacological study by Loevenhart and Grove 

 (1911), intravenous injection into rabbits, cats, and dogs was found to pro- 

 duce a rapid fall in the blood pressure, little change in the cardiac rate, and 

 a decrease in cardiac output with dilation of the heart. o-Iodoxybenzoate 

 acts very similarly but o-iodobenzoate is inactive, indicating that the oxidiz- 

 ing activity is essential. Minimal effects are given in the cat by 13.2 mg 

 (50 //moles), so that the total concentration is probably around 0.5 mM. 

 However, inasmuch as Jahn (1914) showed that blood appreciably reduces 

 the action of o-iodosobenzoate — due to reaction with hemoglobin, other 

 proteins, and glutathione — the concentration of free o-iodosobenzoate is 

 undoubtedly much less. Jahn also showed that the perfused frog heart is 

 depressed by as little as 0.038 mM o-iodosobenzoate and that 0.38 mM 

 causes a prolonged depression of the amplitude, although not standstill or 

 contracture. The results of Mendez (1946) and Mendez and Peralta (1947) 

 on the frog heart differ from those of Jahn, in that concentrations of 0.2- 

 0.4 mM were found to cause an increase in the contractile amplitude, and 

 0.83 mM to produce systolic standstill within 20 min. Furthermore, the 



