Edinburgh.) IN a previous paper, I recorded observations on rabbits and dogs which

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1 THE EFFECT OF ADRENALIN ON SUGAR AND NITROGEN EXCRETION IN THE URINE OF BIRDS. BY D. NOEL PATON.. (From the Research Laboratory of the Royal College of Physicians, Edinburgh.) IN a previous paper, I recorded observations on rabbits and dogs which seemed to prove that the glycosuria induced by the subcutaneous in.jection of adrenalin is essentially a true diabetes. I showed that it is the result of a glycsamia, that it is produced even when the stored carbohydrates have been cleared out of the body by pbloridzin, and that it is accompanied by the disturbances in the distribution of nitrogen in the urine which occur in diabetes. Herter2 has adduced evidence to show that adrenalin acts through the pancreas. His conclusion was based upon the observations that- (a) intra-peritoneal injection of adrenalin acts very powerfully in causing glycosuria, (b) painting adrenalin on the pancreas causes glycosuria, (c) the application of other reducing substances such as cyanide of potassium to the surface of the pancreas causes glycosuria. It is however possible that the substance may be absorbed by the pancreatic blood and may act directly on the liver, although Herter states that the direct injection of adrenalin into that organ did not produce so marked a glycosuria. It appeared to me that the observation of v. Mering and Minkowski3 that the removal of the pancreas in ducks and geese failed to produce diabetes afforded an opportunity of testing whether in all animals adrenalin causes glycosuria through an action on the pancreas. In the present series of experiments I have- 1. Repeated and confirmed v. Mering and Minkowski's observations. This Journal, xxix. p Virch. Arch. LXIX. p Arch. f. exp. Path. xxvi. p

2 60 D. N. PA TON. 2. Investigated the production of injection of adrenalin: glycosuria in birds by the (a) with the pancreas intact. (b) after remrioval of the pancreas. 3. Studied the influence of adrenalin, and incidentally of sulphonal, on the distribution of nitrogen in the urine of birds. Method. An artificial anus was made in a goose or duck just behind the posterior border of the sternum, while the rectal orifice of the cloaca was closed by a series of stitches, thus allowing the urine to be collected apart from the faeces. The animals bore the operation well, and lived for considerable periods. In most of them the bowel was daily cleared by enemata, but in one this was found to be unnecessary as evacuations of the bowel took place spontaneously. The urine was collected during the night by keeping the goose in a cage with a sloping floor opening into a vessel placed below. The floor was kept scrupulously clean and any urine adhering to it was carefully washed off and collected. During the day the goose was allowed to go about and feed in the laboratory and the urine was collected in a tin vessel attached over the cloacal orifice and filled with cotton wadding. Admixture of feeces with the urine was prevented during the course of the experiment by fixing, over the artificial anus a large pad of wadding secured by a leather jacket which prevented the bird removing the pad with its beak. In the ducks no attempt was made to collect the total urine of 24 hours but the animal was allowed to feed from 11 a.m. to 3 p.m. and the urine collected in cotton during the rest of the 24 hours. The urine collected from below the cage was combined with that squeezed from the cotton, poured into a graduated cylinder through a loose filter of glass-wool to catch any feathers or other foreign particles. The wadding was then repeatedly washed in warm water and the washings added to the urine in the cylinder. Finally the wadding was washed in dilute potassic hydrate to dissolve the uric acid still adhering to it and this was poured through the glass-wool plug into the cylinder and the suspended uric acid was in this way dissolved. Acetic acid was at once added. This prevented the loss of ammonia and caused a precipitation of the uric acid in very fine division so that it could be equally distributed throughout the fluid and a fair sample thus secured.

3 ADRENALIN AND URINE Removal of the Pancreas in Ducks. The complete removal of the pancreas is by no means so easy as the description of Minkowski and v. Mering would indicate. To remove 80 to 85 per cent. of the organ is simple, but the remaining part so completely surrounds the nutrient vessels for the duodenal loop of bowel that only by nipping the pancreatic tissue away bit by bit with a pair of narrow-edged dressing forceps was I able to effect a complete removal. In three ducks in which about 80 per cent. of the pancreas was removed and in one in which complete removal was effected no glycosuria supervened. 2. Production of Glycosuria by Adrenalin in Geese and Ducks. (a) With the pancreas intact. In four geese and one duck experimented on, it was founld that, provided they were not much emaciated, the administration of adrenalin chloride in a dose of 1 c.c. of 1 in 1000 adrenalin chloride (Thkamine, Parke, Davis & Co.) per kilo of body weight caused a marked temporary glycosuria. (b) With the pancreas removed. The duck from which the pancreas was completely removed weighed 1750 grms. After the injection of 5 c.cm. adrenalin chloride I in 1000 the urine passed during the succeeding four hours gave a marked and distinct reduction of Fehling's solution. These observations show that in birds at least the glycosuria produced by the administration of adrenalin is not due to an influence upon the pancreas. The fact that, while the islands of Langerhans are well developed, in the duck the pancreas plays no important part in regulating the metabolism of sugar throws doubt upon the theory that the function of these structures even in mammals is to regulate the carbohydrate metabolism. 3. The Influence of Adrenalin and of Sulphonal on the Nitrogenous Metabolism in Birds. It appeared to be of no little interest to ascertain if in birds, which produce uric acid in place of urea as the final product of their nitrogenous metabolism, any disturbance in the distribution of urinary

4 62 D. N. PA TON. nitrogen occurs when adrenalin is given similar to that which is observed in mammals. Normal Distribution of Nitrogen in the Goose and Duck. The previous investigations of Minkowski and of Milroy seem to show that the nitrogen in the urine of the goose is distributed somewhat as follows: in uric acid... about 60 0/0 in ammonia...,, 20/ in other nitrogen..,, 20 /o. Of this " other nitrogen," according to Milroy 's tables, from 10 to 20 is in the form of what he calls " Monamido-nitrogen "-i.e., nitrogen not precipitated by Bohland's phospho-wolframnic and hydrochloric acid mixture. The remaining small amount is in such combinations as the purin bases, the nitrogen of which Milroy finds to constitute a very steady 0002 grm. per diem. Creatinin has not been found in the urine of birds. Methods of Analysis. The urine was collected and prepared in the manner already described. The total nitrogen was determined by Kjeldahl's method in 10 c.cm. of the urine prepared as described. The urea and monamido-acid nitrogen was estimated by precipitating with phosphowolframic and hydrochloric acid and determining the nitrogen of the filtrate. The ammonia nitrogen was determined by Schlbssing's method-50 c.c. being used. The difference between the total nitrogen and the sum of urea nitrogen and ammonia nitrogen may be taken as a measure of the variations in the uric acid nitrogen, since uric acid constitutes nearly 90 0/0 of the whole of this. Exp. I. A goose weighing 5460 grms. had an artificial anus made on Nov. 5th. On Nov. 22nd it weighed 4950 grms. and from the 23rd Nov. to Dec. 5th the urine was collected. It was analysed daily from Nov. 28th to Dec. 5th. On Dec. 6th the goose weighed 4010 grms. Nitrogen in Urine. Bohland Ammonia Uric acid nitrogen nitrogen nitrogen by difference Total Per cent. Per cent. Per cent. Day nitrogen Actual of total Actual of total Actual of total c.c. adrenalin, urine gives reduction. 5 1P c.c. adrenalin, urine gives marked reduction Urine gives slight reduction Urine gives no reduction

5 ADRENALIN AND URINE. Exp. II. A goose weighing 5000 grms. had an artificial anus made on 16th Dec. Its food consisted of 100 grms. Indian meal with 100 grms. of oatmeal per diem but it never took more than about one half of this amount. The urine was collected and analysed from Jan. 7th to Jan. 21st. On Jan. 12th the goose weighed 3400 grms. and on the 22nd 3635 grms. It died on the 26th and nothing abnormal was found on post-mortem examination. Nitrogen in Urine. Bohland Ammonia Uric acid nitrogen nitrogen nitrogen by difference Day Total nitrogen Actual Per cent. of total Actual Per cent. of total Actual Per cent. of total c.c. adrenalin, urine gave very marked reduction Urine gave no reduction gr. sulphonal at 4. Most of it lost gr. sulphonal at 11. Slept all day The results may be shortly tabulated. Average per cent. of total nitrogen in: Urea and monamido-acids Ammonia Uric acid Exp. I. Before After Exp. II. Before After Under sulphonal In these experiments it was found impossible to fix the diet sufficiently rigidly to allow of any conclusion being drawvn as to the influence of adrenalin on the rate of prcteid disintegration. As regards the distribution of nitrogen, the first experiment shows no distinct change in the urea nitrogen, while the second shows a marked increase. The ammonia nitrogen in both experiments is markedly raised, in the first from 12 per cent. to 17 per cent. and in the second from 14 to 19 per cent. 63

6 64 D. N. PA TON. The uric acid nitrogen shows a decrease in the first experiment from 77 to 71 per cent. and in the second from 74 to 65 per cent. Adrenalin in the bird as in the mammal seems to interfere with the synthetic processes carried on in the liver. At the end of the second experiment sulphonal was administered by the stomach tube. Of the dose of 1 grm. given on the 11th day much was lost, but the dose of 2 grms. given on the 12th day was all passed into the stomach. The goose slept for about twelve hours. The urea excretion was somewhat increased. The ammonia excretion was markedly raised, while the uric acid excretion fell to 62 per cent. Sulphonal thus acts on the metabolism in the bird as Eason and I found it to act in the mammall. These observations support the view that uric acid is formed from ammonia compounds, and when considered in connection with Wien er's experiments2, which show that, when a suitable linking acid is supplied, the amount of uirea inje'cted into a bird which can be convetted to uric acid is greatly increased, they point strongly to the conclusion that it is through urea that ammonia is synthesised into the diureides of which uric acid is the chief. CONCLUSIONS. 1. Adrenalin when administered subcutaneously causes glycosuria in birds as in mammals. 2. It does not act through the pancreas. 3. It causes a decrease in the proportion of nitrogen elaborated into uric acid, an increase of the nitrogen in ammonia, and probably an increase in the nitrogen in urea. The expenses of this investigation were defrayed from a donatiorl received from Mr Francis Mason. 1 This Journal, xxvi. p Quoted Maly's Jahresbericht, xxxi. p. 753, 1901.