224 1- lODOACETATE AND lODOACETAMIDE 



cultures is not modified by iodoacetate at 0.25 mM (J. A. Smith, 1958). 

 However, the increase in respiration is reduced. The contractile stimulation 

 by Ca++ is also not affected by iodoacetate (EUis and Anderson, 1951 b). 

 One might expect metabolic inhibition to reduce to some extent cardiac 

 stimulation by drugs, if only by limiting the reserve of energy for accel- 

 erated utilization, but, if the action of a depressant drug is modified, one 

 must assume some more specific mechanism. Iodoacetate was found to alter 

 the response of rabbit atria to acetylcholine in that both the rate and con- 

 tractility are more readily reduced (see accompanying tabulation) (Webb, 



Response to acetylcholine (1 : 10') 

 Rabbit atria 



% Change in rate % Change in amplitude 



Normal - 21 - 63 



Iodoacetate — 37 — 77 



(0.2 mi/, after 16 min) 



Normal — 43 



Iodoacetate — 7 — 62 



(1 mM, after 11 min) 



1950 b). This is not the usual effect of metabolic disturbance on the action 

 of acetylchohne (e.g., fluoroacetate significantly diminishes the response of 

 atria to acetylcholine), nor does it seem likely that under these conditions 

 there could be an appreciable inhibition of cholinesterase. Pyruvate aug- 

 ments slightly the negative inotropic effect of acetylcholine, so that one 

 might suggest that fluoroacetate acts here by reducing the oxidation of 

 pyruvate, but for iodoacetate one must assume some mechanism more re- 

 lated to the EM pathway. 



EFFECTS ON SMOOTH MUSCLES 



Smooth muscles appear to be less sensitive to iodoacetate than are skeletal 

 and cardiac muscle, but occasionally show a very similar type of response, 

 from which one may perhaps gain additional useful information on the 

 general relationship between contractility and glycolysis. Investigations 

 have been unfortunately sparse except for the intestine. 



Gastrointestinal Muscle 



Neuss (1931) was the first to study the intestine and found it to be fairly 

 resistant to bromoacetate; peristaltic movement is stimulated at 0.72 mM 



