Again, the two dinucleotides must have identical phosphoric acid linkages. If linkage (1) exists, linkage (3) must also; if linkage (1) does not exist, linkage (3) cannot. But it was shown in the preceding article that there is no direct phosphoric acid linkage in adenine-uracil dinucleotide and therefore none at the corresponding point in yeast nucleic acid. Hence both linkages (1) and (3) are excluded and there is no direct linkage of phosphoric acid groups in the entire nucleic acid molecule. That the nucleotide groups of yeast nucleic acid (and adenineuracil dinucleotide as well) are not united to one another through their phosphoric acid groups is proven. That this union is through the carbohydrate groups, we conclude from the general principles of physiological chemistry. The combination of purine groups with pyrimidine groups or of either with a carbohydrate group whose aldehyde affinity is already satisfied is very rare in physiological chemistry. But the polysaccharide structure is sufficiently common. It is of course possible to draw other conclusions that can be adjusted to the facts, but they all involve the assumption of curious coincidences and compensations which would cause phosphoric acid to be liberated with equal ease from different kinds of linkage, or that the liberation of phosphoric acid from one kind of linkage is excessively slower than from another. After careful consideration of such matters, we believe we have drawn the correct conclusion. THE INFLUENCE OF INTRAVENOUS INJECTION OF BY SHIGENOBU KURIYAMA. (From the Sheffield Laboratory of Physiological Chemistry, Yale University, New Haven.) (Received for publication, December 11, 1916.) Henderson and Underhill reported that the intravenous injection of peptone into dogs causes hyperglycemia and glycosuria which they considered due to an accompanying acapnia. More recently McGuigan and Ross have stated that peptone administered to dogs intravenously induces a notable hypoglycemia and they ascribe the results obtained by Henderson and Underhill to anesthesia. On the other hand, Glaessner and Pick claim that both pancreatic juice and peptone can inhibit epinephrine glycosuria. If Glaessner and Pick's report is compared with that of McGuigan and Ross, it is possible that the inhibitory influence of peptone upon epinephrine glycosuria may be due to the hypoglycemia. caused by peptone. But it is also possible that peptone decreases the permeability of the kidney for sugar and thus inhibits epinephrine glycosuria, notwithstanding that the blood sugar may or may not be changed simultaneously. Though pancreatic extract has been shown by many investigators to have an inhibitory influence upon epinephrine glycosuria, Leschke demonstrated that an intravenous injection of pancreatic extract alone induces glycosuria. At the suggestion of Professor Frank P. Underhill, I have investigated the effect of peptone injection upon the sugar content of the blood and also upon epinephrine hyperglycemia and glycosuria. Methods. Full-grown rabbits were used. They were fed on oats and corn,, greens being added to the diet from time to time. Water was given freely. The urine was obtained by pressure on the bladder through the abdominal wall. Witte's peptone was always employed in 10 per cent solution in 0.9 per cent sodium chloride solution. Unless otherwise noted, the peptone solution was always sterilized by boiling. Peptone (0.3 to 0.75 gm. per kilo of body weight) was injected into an ear vein without anesthesia. Blood samples for sugar determination were drawn from the other ear. For the control experiments an equal volume of 0.9 per cent sodium chloride solution was used. McGuigan and Ross assert that gelatin and other proteins can cause hypoglycemia as well as peptone. In accordance with this statement some experiments have been made to test the influence of gelatin and egg albumin upon blood sugar content. Commercial gelatin and a preparation of egg albumin were made up to 10 per cent solution with 0.9 per cent sodium chloride solution. The gelatin solution was sterilized by boiling, the egg albumin solution being used without sterilization. When peptone and epinephrine were injected successively, peptone solution was first injected into an ear vein and immediately after that epinephrine (adrenalin chloride 1: 1000 Parke, Davis and Company) was administered subcutaneously. The influence of intravenous injection of gelatin, egg albumin, and also soluble starch upon epinephrine hyperglycemia and glycosuria was studied in some experiments. The methods were the same as described with peptone and epinephrine. Soluble starch (Kahlbaum) was injected in 10 per cent solution, being dissolved in 0.9 per cent sodium chloride solution and sterilized by boiling. In some cases body temperature, respiration, and pulse rate were determined. The body temperature was measured by inserting a thermometer into the rectum after collection of the blood samples. Respiration and pulse rate were measured directly before the taking of a blood sample. The blood sugar was determined by the Lewis-Benedict method, as described by Miss McDanell in this laboratory. The sugar in the urine was estimated by a Schmidt and Haensch triple shadow saccharimeter after removal of the coloring matters and levorotatory substances by a saturated solution of mercuric acetate. Peptone, gelatin, and egg albumin added to the urine were shown not to interfere with this method. For the qualitative tests of sugar in the urine Benedict's reagent was employed. The Influence of Intravenous Injection of Witte's Peptone upon the Sugar Content of the Blood. When Henderson and Underhill injected. Witte's peptone (0.3 to 0.63 gm. per kilo of body weight) intravenously into dogs, the sugar content of the blood increased as high as 0.26 to 0.27 per cent and the urine samples contained large amounts of sugar. McGuigan and Ross also injected Witte's peptone intravenously into dogs, using doses of about 0.12 to 0.66 gm. per kilo of body weight. In their experiments the sugar content of the blood reached a minimum about 2 hours after the peptone injection. The usual result was a fall of the sugar to about one-half or one-third of the original, which in general was much lower than that recorded by other investigators. In some cases they observed a transient and to them insignificant hyperglycemia in the interval between the injection of peptone and the hypoglycemic state; they ascribe this period of hyperglycemia to asphyxial conditions. Henderson and Underhill specifically called attention to the fact that the injection of Witte's peptone induces respiratory disturbances which they ascribed as being the cause of the hyperglycemia and glycosuria present. It is evident that McGuigan and Ross have confirmed the contention of Henderson and Underhill who made no statement concerning blood sugar content or glycosuria after peptone injection so arranged as to have no relation to respiratory disturbances. It is a well known fact that peptone is toxic, when administered intravenously (Underhill, Popielski). Underhill (1903) investigated its behavior with material of both animal and vegetable origin. The susceptibility to peptone is not the same in different species of animals. An intravenous administration of peptone usually brings forth severe toxic symptoms in dogs and sometimes kills the animals even in the dose used by Henderson and Underhill or McGuigan and Ross. The rabbit is usually considered to be less susceptible to peptone. Buchner and Geret reported that an intraperitoneal injection of pure peptone, specially prepared by themselves, in doses of 0.2 gm. per kilo of body weight, killed rabbits within 12 hours. In my own experiments the rabbits usually showed no severe symptoms except a slight degree of prostration after an intravenous injection of Witte's peptone in doses of 0.5 to 0.75 gm. per kilo of body weight. In a few cases 0.5 to 1.0 gm. of Witte's peptone per kilo THE JOURNAL OF BIOLOGICAL CHEMISTRY, VOL. XXIX, NO. 1 of body weight killed the rabbits immediately or in a short time. In such cases prostration, weak heart action, and convulsions were the most noticeable symptoms. The results of the experiments are shown in Table I. TABLE I. The Influence of Intravenous Injection of Witte's Peptone upon the Sugar Content of the Blood. Respiration (R), Pulse Rate (P), and Body Temperature (T). |