Secretin Preparations Research Articles

The preparation of secretin.

The preparation of secretin.

Studies in Pancreatic Function

Summary Norms have been established for the volume, bicarbonate, and amylase responses to a standardized commercially available preparation of secretin. A study of the data has yielded evidence for the use of an 80-minute collection period and for the inclusion of enzyme determinations in the clinical application of the procedure. Body weight adjustment of the values for total volume of secretion and total quantity of amylase results in a marked decrease in the scatter of the data, and therefore, narrowing of the range of normalcy. For this reason, volume and enzyme data should be reduced to a per kilogram basis.

Enzymatic inactivation of secretin.

THE inactivation of secretin by whole blood, cell-free plasma, serum and urine has been demonstrated by Greengard and Ivy1,2 to be an enzymatic process. Because of the stability of their secretin preparations towards crystalline pepsin and trypsin and the absence of detectable proteolytic activity of blood, they concluded that ‘secretinase’ was not a proteolytic enzyme.

Studies in Pancreatic Function

Summary Norms have been established for the volume, bicarbonate, and amylase responses to a standardized commercially available preparation of secretin. A study of the data has yielded evidence for the use of an 80-minute collection period and for the inclusion of enzyme determinations in the clinical application of the procedure. Body weight adjustment of the values for total volume of secretion and total quantity of amylase results in a marked decrease in the scatter of the data, and therefore, narrowing of the range of normalcy. For this reason, volume and enzyme data should be reduced to a per kilogram basis.

The Preparation of Secretin

SummaryA method for the preparation of a potent secretin suitable for intravenous administration in man is described.

The value of an American preparation of secretin in the diagnosis of pancreatic disease

The new Secretin Wyeth is a valuable preparation for the diagnosis in pancreatic disease. It is as potent as the preparations which have been used formerly for the same purpose. It has not the same effect on the bile pigment curve as the Swedish secretin and cannot be employed as a test of gall bladder function.

On the preparation of secretin and pancreozymin.

The Journal of PhysiologyVolume 110, Issue 3-4 p. 367-376 ArticleFree Access On the preparation of secretin and pancreozymin Joan Crick, Joan CrickSearch for more papers by this authorA. A. Harper, A. A. HarperSearch for more papers by this authorH. S. Raper, H. S. RaperSearch for more papers by this author Joan Crick, Joan CrickSearch for more papers by this authorA. A. Harper, A. A. HarperSearch for more papers by this authorH. S. Raper, H. S. RaperSearch for more papers by this author First published: 31 December 1949 https://doi.org/10.1113/jphysiol.1949.sp004445Citations: 67AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume110, Issue3-4December 31, 1949Pages 367-376 RelatedInformation

Effect of Alloxan upon External Secretion of the Pancreas

The report of Goldner and Gomori that in dogs made “diabetic” by alloxan injection the intralobular duct cells of the pancreas showed vacuolization suggested to us the possibility that this might serve as a means of investigating whether these duct cells perform a secretory function. Methods and Results. A standard preparation of secretin concentrate designated S1 was used in these experiments. It is known to contain both secretin and pancreozymin. The particular lot of material used for these experiments was tested on 2 normal dogs and the threshold dose was found to be 0.3 and 0.5 mg respectively, indicating that the material had standard potency. In 4 dogs rendered “diabetic” for 18 to 30 days by the intravenous injection of 75 mg of alloxan per kg of body weight, the threshold dose of this same lot of secretin concentrate was found to be 2, 4, 5 and 10 mg. The “diabetic state” was attested by the strongly positive sugar reaction of the urine accompanied by moderate decline in body weight. Two dogs which were similarly treated with alloxan but failed to become “diabetic” showed a threshold of 0.4 and 0.8 mg secretin concentrate, respectively. In the 2 normal dogs mentioned above, which were used to establish the potency of the secretin preparation, the injection of alloxan in a dose of 75 mg per kg of body weight after the threshold response had been determined did not significantly alter their response to a subsequently administered threshold dose of secretin concentrate within 3 hours. Amylase determinations by the method of Schmidt were performed on all samples of pancreatic juice but revealed no remarkable differences between the juice obtained from alloxan-treated animals and that of normal dogs (Table I). In one animal with alloxan-induced diabetes in which the pancreas was examined histologically, the vacuolization of the intralobular ducts described by Goldner and Gomori was found; the acinar cells were normal.

Assay of Secretin

ConclusionsThe commercial secretin preparation, Pancreotest, has been assayed on dogs and found to be half as potent as our standard material. An apparent discrepancy in the expression of units of secretin has been explained.

Contractions of Frog's Gall Bladder and Its Possible Use as an Assay Method

Contraction of the frog's gall bladder can be readily demonstrated by the intracardiac injection of crude secretin. The frog's gall bladder is usually bluish green, moderately full of bile, pear-shaped, flabby, and is easily observed when the abdomen is opened. After the intracardiac injection of a dilute secretin preparation, there is a latent period of 15 to 100 seconds; the gall bladder then changes to a rounded spherical form, and the organ develops a slight or marked opalescence; the surface may also show a slight or marked puckering; blood vessels over the surface may become tortuous; apparent volume changes may at times be noted. After 2–10 minutes, the surface again becomes smooth, opalescence disappears, and the bladder becomes flabby.The ease with which the above could be duplicated suggested its use as an assay method for substances contracting the gall bladder.A number of preparations have been compared using the following procedures as standard. Active dark colored male frogs weighing 25–35 g...

Auto-Injection of the Biliary Passages from the Gall Bladder in Rabbit

Contraction of the rabbit gall bladder may drive its contents back into the biliary passages if the bile papilla is tonically contracted or if the choledochus is clamped, and dyes previously injected into the gall bladder may then be demonstrated in the liver and arterial blood. Experimental Procedure. 300 mg sodium barbital subcutaneously per kg animal; clamp choledochus; expose gall bladder and withdraw 1 cc of bile; through the same hypo needle kept in situ inject 0.5 cc of 5% sodium fluoresceinate solution; clamp the puncture in the gall bladder by means of a small narrow-jawed bulldog clamp; to contract the gall bladder, 0.5 cc per kg of a crude secretin preparation containing histamin was injected intravenously. Within one or 2 minutes after the secretin injection the gall bladder usually becomes tense, decreases in volume and the choledochus and hepatic ducts appear as bulging, rounded, green cords; the choledochus may be so distended that it is palpable. In 15 minutes approximately some liver lobes may show an irregular yellowish-green mottling on their surfaces. This mottling is generally most marked in the left anterior and posterior lobes and is least in the caudate lobe. At no time was any dye visible in the lymphatics of the gall bladder or the liver hilus. If the animal is now bled to death from the abdominal aorta, the dye may be demonstrated in the serum and the relatively bloodless liver now reveals the dye more clearly than before. If the liver substance is scraped away, scraping from the free border of a lobe toward the hilus, yellow hepatic ducts can be easily demonstrated. These yellowish ducts may often extend practically to the border of the lobe; not all hepatic ducts in any one lobe exhibit the dye, however, and their distribution is irregular.

SECRETIN XI: ITS INFLUENCE ON THE ETICULOCYTES OF THE CIRCULATING BLOOD*

An increase in the red blood corpuscle count after the injection of secretin preparations has been reported a number of times in the literature.1, 2, 3 According to King4 no significant change occurred in the reticulocyte count after the injection of a secretin preparation. However, within the last few years progress has been made in extracting a more highly purified product and it appeared that it would be of interest to isolate the fraction responsible for the increase in the number of red blood corpuscles in a unit volume of blood and to study this portion with respect to any possible effect that it might have on the number of reticulocytes in the circulating blood. In the following work we prepared an extract of the small intestine following the method of Ivy, Kloster, Lueth and Drewyer5, which they designate ApH 1802. A saturated solution of this preparation in 0.9 per cent sodium chloride solution was injected subcutaneously into rabbits and guinea pigs; 1 cc. per kg. body weight being used. Rabbits have been used by a number of investigators of the problem of the effect of secretin preparations on the formed elements of the blood,but it was considered advisable to determine its effect on guinea pigs also in view of the work of Jacobson6 which suggests that the response of the guinea pig to liver extract may serve as a quantitative assay of its therapeutic potency. Blood was drawn from the ear vein and two slides prepared according to the method of Cunningham.7 Two thousand cells were counted in each instance.

SEGRETIN: ITS INFLUENCE ON THE AMOUNT OF HEMOGLOBIN IX THE CIRCULATING BLOOD

Various investigators (Downs and Eddy, 1; King, 2) have reported an increase in the corpuscle count of the circulating blood after the injection of a secretin preparation. However, as far as we are aware the hemoglobin content has not been determined under these circumstances. The present report embodies results of experiments on rabbits which seem to show that secretin injections increase the hemoglobin in the blood stream. Two different extracts were used. The first was prepared from the intestine of the dog by the ApH 1802 method of Ivy, Kloster, Luett and Drewyer (3), the significant results of which are shown in Table I. The

Secretin

The preparation of secretin has been described in a previous paper (1928). The method involved extraction of the duodenal mucosa with absolute alcohol and precipitation of the dissolved secretin by bile salts. It was based on two observations: ( a ) secretin exists in the duodenal mucosa in an active condition, and ( b ) the secretion of pancreatic juice is due primarily to the absorption of bile salts in the duodenum. The bile salt used in the precipitation of secretin was commercial sodium tauroglycocholate. Apparently many varieties of this commercial bile salt preparation exist depending on the type of bile from which it has been obtained. For this reason many experimenters have experienced difficulties in obtaining satisfactory yields of secretin by this method. The conditions under which pure taurocholic acid precipitates secretin from solution have been worked out, but since this bile acid is difficult to obtain the results are of small general interest. For these reasons the preparation of secretin by a method which requires no special reagents is described. The description is divided into three stages. At each of these stages the preparation may be left for some days without deterioration. (1) The duodenum and upper part of the jejunum ( i. e. , 3 feet of gut from the pyloric sphincter) of the recently killed pig is used as the source of the secretin. The mucous membrane is scraped off within 3 hours of the death of the animal, ground up with sand, and extracted with a volume of ethyl alcohol equal to four times its weight. The mixture is well shaken, allowed to extract at room temperature for 30 minutes and then filtered. The clear filtrate, if kept in the dark in a cool place, retains its activity for several days. It may be observed that a solution of secretin containing bile pigment is destroyed rapidly by light.

Mechanism of Secretin Diuresis.

Owen and Ivy have shown that the intravenous injection of concentrated vasodilatin-free secretin preparations into dogs results in a typical moderate diuresis. Certain characteristics of the diuresis led us to suspect that it was related to, and probably dependent upon the secretory stimulation of pancreatic juice and bile. The following experiments give evidence that this is the case. Following pancreatectomy and ligation of the common bile duct, previously active preparations are without effect on the rate of urine flow. Secretin preparations cause no diuresis if the bile and pancreatic juice resulting from their injection are diverted from the intestine by cannulae. Reintroduction of the collected bile and pancreatic juice into the intestine is followed by the typical diuresis. Diuresis in the intact dog is therefore dependent on the secretion of pancreatic juice and bile, and the entrance of these secretions into the intestine where they may be reabsorbed. It may be noted that in the experiments in which Mellanby reported that secretin had no diuretic effect, the pancreatic juice and bile were simultaneously collected by means of cannulae so that they could not enter the intestine.

On the preparation of secretin

On the preparation of secretin