724 PRINCIPLES OF GENERAL PHYSIOLOGY 



concerned with inhibition are not identical, in their relations to chemical sub- 

 stances, with those concerned with excitatory effects. Ergotoxine, as we shall 

 see presently, is of interest in this respect. 



It is difficult to reconcile the view that the sympathetic nerves produce their 

 effect by the liberation of adrenaline at the myo-neural junction with the fact 

 that a base, which only differs from adrenaline by the absence of the methylation 

 of the amino group, is as active. Why should it set free an allied substance, 

 but not a more active one? The difficulty is further increased by the fact that 

 certain inhibitory effects, as on the non-pregnant uterus of the cat, are relatively 

 more easily produced by adrenaline than by nerve stimulation, whereas some 

 motor effects, such as pilo-motor action, are more easily produced by nerve 

 stimulation than by adrenaline. 



The fact that these bases have very definite relations to the cells .of a certain 

 morphological system shows that there "must be something in these cells, or 

 connected with them and them only, which has a strong affinity for these amines." 

 But it is pointed out that this property is by no means necessarily the same 

 as that which confers stimulant activity on the amines. As I pointed out in 

 connection with catalytic action, the adsorption of a substance on a surface 

 is independent of the chemical action it may exert on the material of the 

 surface after adsorption. Barger and Dale further call attention to atropine 

 and pilocarpine, whose localisation is practically identical, while their action 

 is opposite. Thus also the peculiar distribution of the action of nicotine, or 

 of the sympathomimetic amines, does not necessarily depend on the existence 

 of specific chemical receptors in the cells peculiarly sensitive to them. It may 

 be that in some cells the stimulant substance easily reaches the site of action. 

 The authors further find "the theory of receptive side-chains very difficult to 

 apply " to their results. If the relation is one of chemical union, it seems that 

 the points of constitution common to all the active bases should give an 

 indication of the nature of the chemical receptor in the cells which combines 

 with them. But there is only one common complex, namely : 



I I I 

 C C N, 



I I I 



and this "exists in innumerable bases with no sympathomimetic activity." 

 That physical factors intervene is indicated by the fact that differences in 

 the relative activity of pairs of substances appear in the course of an experiment, 

 and occasionally in an individual cat as compared with other cats. On the purely 

 chemical view, it would be necessary to assume that there is a different chemo- 

 receptor for each amine, and that these may vary independently of each other ; 

 a view very difficult to maintain, since " the number of possible sympathomimetic 

 amines is indefinitely large." The conclusion arrived at is that " the least 

 unsatisfactory view seems to us to be that which regards the existence of 

 stimulant activity as dependent on the possession of some chemical property, 

 the distribution and, in the main, the intensity of activity as due to a physical 

 property." 



The remarks of Straub (1912, p. 4) are also of interest. "The theory of the 

 selective distribution of active substances in the organism has, as a necessary 

 foundation, a purely material taking up of them by the cell. What happens in 

 the cell in presence of the substance, how it gets there, and why it is held fast is 

 the next question. It is frequently answered (as by Ehrlich) by the statement 

 that the substance, as a chemical individual, reacts with chemical constituents of 

 the chosen cell, with satisfaction of affinities and formation of a chemical compound. 

 I hold this explanation, in its general aspect, as too far-reaching and inappropriate, 

 and, in its results, as unfruitful. There are an indefinite number of substances 

 which have a constitution scarcely capable of reactions in the organism, such as 

 nitrous oxide, carbon dioxide, potassium salts, and many of those substances 

 called indifferent narcotics, on account of their passivity ; one cannot imagine with 

 what cell molecules they are*to show chemical affinity, since this affinity of the cell 

 molecules arises merely from ordinary organic chemistry. If one is to operate 



