EFFECTS ON- SMOOTH MUSCLES 225 



and higher concentrations, but to produce contracture 720 mM is required. 

 Atropine does not prevent these effects and thus they are not mediated 

 through the vagus. Intestine poisoned with 7.2 mil/ bromoacetate responds 

 normally to acetylcholine and histamine. Intestinal muscle contains a very 

 ])oor store of carbohydrate but, when supplied with glucose, exhibits a 

 fairly high rate of glycolysis, which is increased by stimulation of the in- 

 testine. One might expect iodoacetate to depress intestine when the meta- 

 bolic basis for its functioning is glycolytic. Prasad (1935 a) found that 0.54 

 mM iodoacetate has no effect on rabbit ileum aerobically, but muscle be- 

 haves much like skeletal muscle in this respect. It was also shown that 

 glycolysis is well inhibited by iodoacetate at this concentration. Rigor de- 

 velops soon after spontaneous movement ceases. Pyruvate is able to stim- 

 ulate iodoacetate-treated intestine, but glucose and lactate are ineffective 

 (Prasad, 1935 b). Prasad also pointed out that the levels of creatine-P and 

 ATP in intestinal muscle are low, so that rigor occurs rapidly when all 

 sources of ATP synthesis are blocked. 



Rabbit intestine is stimulated by glucose and pyruvate. Iodoacetate at 

 1 mil/ has little effect on the intestine in glucose-free medium, but prevents 

 the stimulation by glucose without interfering with the stimulation by py- 

 ruvate (Feldberg, 1943). Indeed, glucose usually causes some depression 

 in the presence of iodoacetate, an effect occasionally observed in other tis- 

 sues, which could be due to the accelerated depletion of ATP through the 

 formation of hexose-P's. 



Although the response of rabbit intestine to acetylcholine aerobically is 

 not prevented by iodoacetate (Porro, 1955), anaerobically it is completely 

 abolished (West et al, 1951). The development of rigor anaerobically can 

 be partially reversed by oxygen, leading to the conclusion that restoration 

 of some ability to form ATP counteracts the process of rigor, although not 

 necessarily reversing it when it is fully developed. Goodman and Hiatt 

 (1964) give the iodoacetamide concentration to prevent acetylchoHne stim- 

 ulation of rat intestine as 5.7 milf , at which time 75% of the tissue SH 

 groups are alkylated, this confirming the insensitivity of the intestine; how- 

 ever, interference with the acetylcholine response must occur at much 

 lower concentrations, as shown with other SH reagents. 



The tension of guinea pig taenia coli is slowly reduced by 1 mM iodo- 

 acetate and eventual failure occurs in a relaxed state (Biilbring and Liill- 

 mann, 1957). There is no dissociation of electrical activity and the tension, 

 the resting membrane potential is not altered significantly, and the spike 

 frequency is slowed and becomes irregular. At low concentrations, around 

 0.02 mM, iodoacetate in common with other inhibitors initially increases 

 the spike frequency (Axelsson and Biilbring, 1961). At this concentration 

 iodoacetate is able to prevent the normal response to a sudden rise in the 

 temperature (disappearance of spikes). Since phosphorylase activity is in- 



