lllSTOLOtiY OF TIIK POISON-CLANDS <!' HU''<> ACIA. S.t 



the glandular epithelium to make the- venom, a mother substance is formed which is later 

 activated in the mature gland-sac to the chromaphil adrenalin through the agency of the 

 naked nuclei of the gland-wall. Most authors who have worked with poison glands of 

 Hatrachia are of the opinion that the venom is the result of nuclear activity, since the cyto- 

 plasm of the gland-cells could never account for the amount of secretion in the mature gland 

 or its increase after the cytoplasmic destruction leaves the wall of the gland, lined with 

 naked nuclei alone. Madame Phisalix, who studied the glands of the salamander, describes 

 the nuclei as actively engaged in the production of poison grains. It is not probable that 

 the nuclei can produce the secretion entire, since in that case we might expect discharged 

 glands to refill, as the naked nuclei seem uninjured in the expulsion of the secretion and 

 there is no evidence that such refilling ever takes place, the emptied gland degenerating and 

 being at once absorbed. 



Unfortunately nothing is known about the origin of adrenalin in the organs in which 

 it is commonly found and it is only recently that its chemical structure and position have 

 been recognized. It is an aromatic amine base and its identification as such has stimulated 

 the interest of investigators in other substances belonging to this group. Their work 

 (pharmacological and chemical) has resulted in a fairly extensive knowledge of the origin, 

 occurrence, and behavior of some of these compounds. In general, it may be said that 

 these amine bases have a pressor effect on the circulation, and that the more nearly they 

 are related chemically to adrenalin, the more closely they resemble it in their pharmacolog- 

 ical effect on animals. In other words, in this group of compounds chemical and physio- 

 logical similarity go hand in hand. They resemble each other also in another way, since 

 it has been shown that different amin bases are derived in the same manner from closely 

 related ammo-acids. Recently some interesting facts have come to light about the origin 

 of certain members of this class which we believe to be significant, and to have a distinct 

 bearing on the question we have been considering, namely, the origin of cpinephrin in the 

 poison-glands of Bufo agua. 



Barger and Walpole (1909) have isolated a poisonous pressor base p-hydroxyphenyl- 

 ethylamin, from putrefying horse meat, which is very closely related chemically and physio- 



HO 



logically to epinephrin, H0< >CH (OH) CH 2 NH. C'H 3 . 



This base has the formula HO/ ^X'H 2 CH,. NH 2 



and is derived from the amino-acid, tyrosin, HO<^ /CH 2 ( 'H (NILi ('((Oil. one 



of the commonest products of protein decomposition, through the agency of certain 

 putrefactive bacteria, which split off CO 2 from the tyrosin molecule. The same base is 

 similarly formed from tyrosin by yeasts during the ripening of cheese, and Barger and 

 Dale (1909) have obtained it from ergot and have shown that it is responsible for some 

 of the physiological effects of that drug. Emerson (1902) found the substance in pieces 

 of pancreas autolyzed under supposedly aseptic conditions and was able to increase the 

 amount formed in his preparations by adding pure tyrosin to them, but Alxlerhalden 

 (1909) was unable to confirm his results and it is probable that Emerson's material 

 became in some way infected. Thus, p-hydroxyphenylethylamin is always produced in 

 nature as a result of cellular activity from tyrosin, one of the end-products of protein 

 decomposition. 



