PROTAMINS AND HISTONS. 433 



agglutination of corpuscles together with the decrease in leucocytes 

 is no wise different from that of the protamins. This interesting 

 fact is readily explainable when it is remembered that the histons are 

 in all probability compounds of protamins and proteids. According 

 to Bang^ the nucleoproteid from the pancreas and its cleavage product 

 guanylic acid possess a physiological action not unlike that of histon 

 and protamin. 



The physiological action of protamins has been the subject of a care- 

 ful study by Thompson^ who showed that clupein and salmin, which 

 are probably identical, and scombrin show no difference in their 

 effects whereas the more complex sturin is somewhat less poisonous. 

 A marked and relatively rapid fall in blood pressure was observed 

 shortly after the injection of the protamins. In dogs death rapidly 

 followed if the dose exceeded 0.15-0.18 g. of clupein per 10 kilo- 

 grams of body weight. The limit in the case of sturin was about 

 0.20—0.25 g. With non-fatal doses the blood pressure returns to 

 the normal in about half an hour and a subsequent injection of an 

 otherwise fatal dose is tolerated. According to Thompson the pro- 

 tamins, like the albumoses, act directly upon the walls of the blood- 

 vessels. The effect upon the respiration is extremely marked and 

 when death occurs it is due to paralysis of the respiratory move- 

 ments. The drop in the blood pressure is accompanied by an in- 

 crease in the depth and frequency of both the abdominal and thoracic 

 respiratory movements. During the period of minimum blood 

 pressure the respiratory movements cease. With the rise in pressure 

 the abdominal respiration is resumed but the thoracic movements are 

 held in check as long as the poison continues to act. The effect upon 

 the coagulation of blood was also shown to be marked. While a 

 single injection shows but little effect, two or three injections delay 

 the coagulation for many hours. A retardation was also observed 

 when the blood was added to protamin in a test-tube. It is worthy 

 of note that the blood became more transparent, and granular. The 

 corpuscles thus agglutinated settle rapidly, leaving a clear supernatant 

 plasma. In this respect the protamins behave like albumose, histon, 

 venoms, ricin, guanylic acid and other agglutinants. The number of 

 circulating leucocytes was appreciably decreased. 



From the above it is evident that the protamins and histons are 

 active poisons. The toxicity is connected with the protamin mole- 

 cule as a whole inasmuch as it disappears completely on cleavage. 

 Thus, the very earliest hydrolytic products, the proton, or pepton of 

 the protamins, exerts but very little effect in 0.5 g. doses, and the 

 final products of cleavage, the hexon bases, according to Thomson 

 show no action whatsoever upon the blood pressure or upon the 

 respiration. Arginin and histidin, like antipepton, hasten the coag- 



• Zeiis. phyml. Ohem., 32, 201, 1901. 

 2 Zeits. physiol. Ohm., 29, 1, 1900. 



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