258 PROFESSOR RUTHERFORD ON THE 
MopeE or ACTION oF HEPATIC STIMULANTS. 
Although we have definitely proved that a large number of substances 
stimulate the liver to secrete more bile, we do not profess to have absolutely 
shown in what manner they do this. It may be asked— 
1. Do they excite the mucous membrane of the duodenum or other part of 
the small intestine, and thereby induce reflex excitement of the liver? One 
would be readily disposed to entertain this idea from the fact that stimulation 
of the oral mucous membrane so readily induces secretion in the salivary 
glands; yet we are obliged to reject the idea that this likewise holds true of 
the liver, because such substances as gamboge and magnesium sulphate power- 
fully irritate the intestinal mucous membrane, while they do not in the least 
increase the secretion of bile. On the other hand, such substances as ipecacuan, 
sodium benzoate, and ammonium benzoate powerfully excite the liver without 
inducing any notable excitement of the intestine. 
2. Do these substances stimulate the hepatic cells by merely increasing the 
stream of blood through the liver? Whatever be the state of the hepatic 
vessels during increase of the biliary secretion, it is quite certain that increased 
secretion of bile does not necessarily follow dilatation of the intestinal capillaries; 
the effect of which, if it be not carried to excess, may with reason be supposed 
to increase the stream of blood through the portal vein, and thence through the 
liver. But castor-oil greatly dilates the intestinal capillaries, yet the bile- 
secretion does not rise in the least. 
3. We therefore believe that the effect of hepatic stimulants is to be assigned 
to a direct action of their molecules upon the hepatic cells or their nerves. The 
effect of physostigma and atropia rather points to an action on the latter—in 
their instance, at all events—as has been already indicated (p. 210). But we 
do not think it advisable at present to pursue this difficult subject, which, as 
far as we can see, is of little importance compared with knowing what does and 
what does not stimulate the liver. 
It is particularly to be observed that all our experiments concern the influ- 
ence of substances on the bi/e-secreting mechanism. The nature of our method 
has forbidden any observations on the action of drugs on the bi/le-expelling 
mechanism. Seeing that the acid chyme, by irritating the duodenal mucous 
membrane, effects a reflex expulsion of bile, it may be that many substances 
which stimulate the duodenum have a similar effect. Yet we cannot but think — 
that to bring about an expulsion of bile by muscular contraction of the gall- 
bladder and bile-ducts is, in all probability, a small thing when compared with — 
increasing the secretion of bile. One might expect that such powerful intestinal — 
irritants as magnesium sulphate and gamboge would be likely to bring about a _ 
