258 INTERNAL SECRETION 



substance, to a certain extent, blocks its own passage into the 

 general circulation. It is able to overcome, to a very small extent 

 only, the resistance produced by the extreme contraction of the 

 vessel walls ; thus the major portion of the substance passes 

 gradually, by a process of diffusion, into the surrounding tissue. 



Elliott, whose experiments confirmed those of Carnot and 

 Josserand, holds the view that the disappearance of adrenalin from 

 the blood is in direct ratio to the development of its effects in the 

 tissues. That a comparatively small amount of adrenalin dis- 

 appears in the liver, in spite of the large amount of tissue which 

 that organ contains, is probably explained by the fact that the 

 vaso-constrictor effect produced by adrenalin in the liver is also 

 comparatively small. 



Although these observations seem to point to the fact that 

 adrenalin is used up and destroyed by the tissue elements which 

 it excites, they do not supply a sufficient explanation of the 

 transience of the 'effect of large doses of adrenalin. 



It has been shown by experiments of the most varied descrip- 

 tion that, after the specific action of adrenalin has passed off, the 

 substance has not by any means disappeared from the blood. 

 Weiss and Harris injected adrenalin into the general circulation 

 of frogs after ligature of one iliac artery and observed the results 

 in the webs of both feet. After the vaso-constriction had entirely 

 passed off in the w r eb of one foot, they removed the ligature from 

 the artery and found that intense vaso-constriction appeared in 

 the web of the other. These authors, similarly to Ehrmann and 

 Miller, also found that blood taken from an animal after the 

 effects of adrenalin had passed off, could be used to produce 

 hypertension in a second animal. 



These observations show beyond all doubt that, after its 

 introduction into the blood-stream, adrenalin neither disappears 

 nor does it undergo any depreciation of its pharmacodynamic 

 value. 



In face of this fact, the question as to the mechanism by 

 which adrenalin achieves its effect requires further consideration. 

 The experiments of Straub and Kretschmer, which supply evi- 

 dence of the most valuable description concerning the part played 

 by adrenalin in the physiology of the organism, also throw im- 

 portant light upon this matter. 



These experiments are based upon facts supplied by Straub 

 concerning the mechanism by which the effects of muscarin are 

 brought about. These facts are as follows :- 



(1) A toxin which has already penetrated the cell which has a 

 specific sensibility to it, is inactive. 



(2) A toxin which has not as yet penetrated such a specific 

 sensitive cell, is also inactive. 



(3) It is only in the course of, and by means of, the penetration 

 of the toxin into the cell, that the specific toxic action takes place. 



The observations, to which reference has been already made, 



