CHEMICAL CORRELATION OF PROCESSES OF DIGESTION 373 



The immediate origin of this phenomenon resides in the acidity of 

 the gastric contents which, upon the opening of the pylorus, come in 

 contact with the mucosa of the upper part of the duodenum, and, in 

 fact, a copious secretion of pancreatic juice may be elicited by simply 

 bathing the duodenum with dilute acids, for example 0.4 per cent, 

 hydrochloric acid. The same result is obtained if the acid be intro- 

 duced into the jejunum, but not when it is introduced into the ileum. 

 The exciting agent, however, is not the acid itself, for the injection of 

 0.4 per cent, hydrochloric acid (one-tenth normal) into the circulation 

 is without effect upon the secretion of pancreatic juice. The excitation 

 of the pancreas is, on the other hand, not accomplished through a 

 nervous reflex because it occurs, and is undiminished when the portion 

 of the intestine which is treated with acid is isolated from all nervous 

 connections, and furthermore, it continues after the administration of 

 Atropine, which paralyzes the endings of the secretomotor nerves. 



The actual intermediary which brings about this correlation is a 

 substance Prosecretin which is present in the mucous membrane of the 

 duodenum and the jejunum, and which is changed by acids into 

 Secretin, a diffusible, water-soluble, heat-resistant substance, which has 

 the property of specifically stimulating the secretory cells of the 

 pancreas. If the mucous membrane be scraped from the surface of the 

 duodenum and rubbed up in physiological saline solution (0.9 per cent. 

 NaCl) the filtered extract which is thus obtained may be injected into 

 the circulation without eliciting any secretion of pancreatic juice. If, 

 however, the extract be previously boiled, or acidified and then 

 neutralized, the injection will now be followed by a copious secretion 

 of pancreatic juice. In normal digestion the transformation of the 

 prosecretin in the duodenal mucosa into secretin is accomplished by 

 the acid chyme, and the secretin which is formed is carried by the blood- 

 stream to the cells of the pancreas. 



Secretin occurs in the mucosa of the intestine in all vertebrates and 

 even in the intestines of fishes. It is diffusible, is not destroyed by 

 boiling, and is soluble in acidified solutions of mercuric chloride, being 

 precipitated on neutralization. It appears to be a nitrogenous base, 

 and is probably an amine derived by Decarboxylization from an amino- 

 acid or from an amino-acid derivative. Acidified extracts of the 

 intestinal mucosa and of many other tissues, contain /3-Iminazolyl 

 Ethylamine but this substance is devoid of action upon the secreting 

 cells of the pancreas. The chemical identity of secretin has therefore 

 not been established. A nitrogenous base having a similar action upon 

 the pancreas is known, however, namely Pilocarpine, a trimethyl 

 ammonium derivative obtained from the leaves of Pilocarpus jaborandi. 



It must be stated, however, that acids are not the only substances 

 which will bring about a secretion of pancreatic juice when they come 

 into contact with the duodenal mucosa. Fats are particularly active 

 in causing secretion of the pancreatic juice after their entry into the 

 duodenum, probably, however, only after they have been partially 



