142 



Fig. 9. Three arrangements of receptor relative to enzyme for the acetylcholine 

 system are shown: on the left, the enzyme is just outside the receptor; center, enzyme 

 is just inside; and right, areas of receptor and enzyme alternate over the membrane 

 surface. Arrows indicate direction of diffusion of ACh. 



would hardly seem to be much functional significance in this arrangement 

 because the concentrations of ACh are so small and the material is diffusing 

 into an almost infinite volume of cytoplasm. In (c) the effect would be that of 

 saying that a greater or lesser area of the membrane is inactive in the sense of 

 being a receptor, since it is given over to enzyme action. Fig. 9 shows the three 

 arrangements discussed. 



A decision as to the extent of the coupling between enzyme and receptor 

 can be based on studies of specific inhibitors of the enzyme. If the inhibitor is 

 a substance that reacts solely with the enzyme, its introduction should result 

 in the persistence of ACh for a longer period of time at the receptor, or the 

 escape of ACh should now be diffusion limited. If receptor and enzyme are 

 both consequences of membrane structure, a block of the enzyme may result 

 in the production of more receptors as well as a persistence of ACh at the mem- 

 brane; the experimental problem is then, to distinguish between persistence of 

 ACh and an actual increase in the number of receptors. According to conven- 

 tional explanations of the action of ACh-ase inhibitors several points are not 

 clear. On peripheral nerve, inhibitors (such as DFP) depress conduction to the 

 point of failure (Crescitelli et al, 1946) while at the n-m-j the first action of 

 inhibitors is to facilitate excitation. In the arthropods where ACh cannot be 

 demonstrated to exert a physiological action (Prosser, 1952), inhibitors excite. 

 All of these excitable systems have ACh-ase activity and the apparent differ- 

 ences between them can be explained by assuming that nerve does not have 

 ACh receptors (as it is excited by a K+-Na + mechanism) , while arthropods have 

 a transmitter that differs in some respects from ACh. The suggestion has been 

 made several times, most recently by Zupancic (1953), that receptor and 

 enzyme for the ACh system are in fact identical, but the information used to 

 support such claims has not generally been able to dispose of the objection 

 that certain substances are rather selectively reactive with either enzyme or 

 receptor. The evidence to be presented here is not that receptor and enzyme 

 are identical but that they are both aspects of the activity to be expected 

 from a membrane based on previously discussed structural considerations. 



