NERVOUS ACTION 



In view of the hi<7h nfrmity of eserine for choline esterase, the 

 enhancing effect of tiiis compound on nerve stimulation, the third 

 kind of evidence which was considered as essential, may well be at- 

 tributed to the inhibition of choline esterase. But here again no 

 conclusion is possible as to the mode of action of acetylcholine. The 

 enzyme outside the cell will probably be inhibited; but a fraction of 

 the inhibitor may enter the cell. In both cases an enhancing effect of 

 nerve stimulation may result. Such an effect does, therefore, not per- 

 mit any conclusion as to whether acetylcholine acts physiologically 

 inside or outside the cell. There may be, also, no enhancing effect at 

 all, or it may be difficult to obtain, as in the case of the superior cervical 

 ganglion — a fact which appeared so puzzling to Dale. 



We now arrive at a fundamental difference between the implica- 

 tions based on methods of enzyme chemistry and those based on 

 pharmacological tests. All facts observed on choline esterase point 

 unequivocally to the same role of acetylcholine in all nerves. All 

 contain the same specific enzyme, whether they belong to invertebrates 

 or vertebrates, to mammals or to fish. All contain a high concentration 

 of choline esterase whether sympathetic or parasympathetic, auto- 

 nomic or central nervous system, efferent or afferent. This con- 

 centration probably varies because the active surface per unit of tis- 

 sue varies. Other factors may also be important; but the order 

 of magnitude is always the same and sufficient to permit the assumption 

 that the substrate is metabolized at a rate parallel to that of the electric 

 changes, that is, the passage of the impulse. There are other indica- 

 tions. Wherever tested, a coincidence was found between the time of 

 appearance of the high enzyme concentration and the beginning of 

 nervous function during growth. The possibility of applying findings 

 obtained with the electric organ to the mechanism in brain, as illus- 

 trated by the discovery of choline acetylase, is another example. So far, 

 no biochemical fact has been found which is not consistent with the 

 conclusion that acetylcholine has the same function in all nerves. It is 

 difficult to conceive that such a specific and well-defined mechanism 

 either should have a variety of functions in different nerves or, as the 

 only other alternative, should be active in some, and inactive — although 

 present — in other nerves. 



In striking contrast to the uniformity of the enzymic mecha- 

 nism, we find a great variety of effects if the pharmacological 



