Rate and pattern of disappearance of exogenous gastrin in dogs

Dd, Reeder; Bm, Jackson; En, Brandt; Jc, Thompson

doi:10.1152/ajplegacy.1972.222.6.1571

Cited by 26 publications

(8 citation statements)

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“…The metabolic clearance rate, an expression of the rate of catabolism during infusion, decreased significantly after nephrectomy at both infusion rates. These observations indicate that the kidney is an important organ for the catabolism of exogenous gastrin.Synthetic human gastrin I has been shown to have a short half-life when it is infused into dogs (Reeder, Jackson, Brandt, and Thompson, 1972b). This is in accordance with the brief physiological action that infusions of gastrin II have in man (Makhlouf, McManus, and Card, 1966).…”

supporting

confidence: 57%

Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

Bg¹,

Dd²,

En³

et al. 1973

Gut

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SUMMARY Studies of gastrin metabolism were performed in four dogs before and after nephrectomy. Synthetic human gastrin I was infused for two hours and serum samples were obtained at various times during and after infusion. Serum concentrations of gastrin were measured by radioimmunoassay. A two-compartment model was employed to calculate half-lives under each of four experimental conditions, low and high infusion rates, used both before and after nephrectomy. The model half-life was greatly prolonged after nephrectomy at both infusion rates (from 2.54 min to 5.15 min at the low rate, and from 2.85 min to 7.88 min at the high rate). The metabolic clearance rate, an expression of the rate of catabolism during infusion, decreased significantly after nephrectomy at both infusion rates. These observations indicate that the kidney is an important organ for the catabolism of exogenous gastrin.Synthetic human gastrin I has been shown to have a short half-life when it is infused into dogs (Reeder, Jackson, Brandt, and Thompson, 1972b). This is in accordance with the brief physiological action that infusions of gastrin II have in man (Makhlouf, McManus, and Card, 1966).Evidence has been presented that in dogs synthetic human gastrin may be inactivated in vivo by the kidney (Clendinnen, Davidson, Reeder, Jackson, and Thompson, 1969) and the liver (Thompson, Reeder, Davidson, Charters, Bruckner, Lemmi, and Miller, 1969), and in vitro by the lung, skeletal muscle, and gastric fundus mucosa (Thompson, Reeder, Davidson, Jackson, and Clendinnen, in press). Of these sites the kidney is believed to be the most efficient (Clendinnen et al, 1969).The effect of nephrectomy on the half-life of circulating exogenous gastrin in dogs has been determined by measuring the rate of disappearance MethodSynthetic human gastrin I was infused in four healthy, alert mongrel dogs weighing 17-22 kg. A catheter for infusion was placed in the superior vena cava and a catheter for sampling was inserted in the iliac vein. Synthetic human gastrin I was given to the fasting dogs according to two dosage regimens. The low dose consisted of a loading injection of 4 micrograms (pg), followed immediately by infusion at the rate of400 nanograms (ng)/kg/hour for two hours. The high dose was 8 ,ug given as a load and 800 ng/kg/hour infused for two hours. These two infusions, given in random order, were separated by a rest period of two days. Infusion of gastrin at these rates resulted in nearly constant values for serum gastrin after one hour. Two basal serum samples for gastrin measurement were obtained before the administration of exogenous gastrin. Additional samples were obtained at the end of the infusion (time zero), and at one, two, three, four, five, eight, 10, 15, 30, and 60 minutes thereafter. One week after the completion of these experiments, both kidneys were removed under general anaesthesia. The dogs were then allowed to recover for two days 462 on 12 May 2018 by guest. Protected by copyright.

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supporting

confidence: 57%

Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

Bg¹,

Dd²,

En³

et al. 1973

Gut

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“…8). For comparing the halflife of secretin it is necessary to fix certain points [18,20] or to use the method described by M a k h l o u f [22] and R eeder et al [28] calculating the rate of disappearance of gastrin from the circulating blood.…”

Section: Biological Half-live O F Secretin After Ligature O F Renal Bmentioning

confidence: 99%

Studies on the Elimination of Secretin and Cholecystokinin with Regard to the Kinetics of Exocrine Pancreatic Secretion

Lehnert¹,

Stahlheber²,

Forell³

et al. 1974

Digestion

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Studies were performed on 72 anesthetized mongrel dogs. Upon injection or infusion of secretin into the portal vein, the pancreatic volume and bicarbonate response was found to be significantly smaller than following administration into the femoral vein, but only when low doses of secretin (0.25 clin U/kg/h or smaller) were applied. No difference was observed in pancreatic protein and enzyme secretion after cholecystokinin, when both high and low doses were applied to the portal or femoral vein. The injection of secretin and cholecystokinin into the renal artery causes a loss of biological activity of 75 and 60%, respectively, as compared to femoral administration. Ligature of the blood vessels of both kidneys resulted in an increase in the biological activity of secretin of 80% and of cholecystokinin of 50%. The slopes of the flow rate curves determined upon secretin injection were smaller after ligature of the renal blood vessels. The biological half-life of secretin increased from an average of 2.9 to 4.8 min. These results indicate that the kidneys play a role in the catabolism of exogenous secretin and cholecystokinin, whereas the blood and the liver (at least for cholecystokinin) seem to be of small importance.

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“…Disappearance half-time measurements of each of the different molecular forms of gastrin available in a pure state are related to their molecular size: tridecapeptide gastrin (G-13-I, MW 1647, Ti = 1 8 minutes ); heptadecapeptide gastrin (G-17-I, MW'2096, Ti = 2-1 minutes (Reeder et al, 1972)); big gastrin (G-34-I, MW 3839, Ti = 9 minutes (Straus and Yalow, 1974), Ti = 15 minutes ). The disappearance half-time of endogenous antral gastrin in dogs measured by Thompson et al (1975) was 8-6 minutes, which presumably represents the half-time of the mixture of molecular forms of gastrin circulating in peripheral blood.…”

mentioning

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Disappearance half-time of endogenous and exogenous secretin in dogs.

Curtis¹,

Fender²,

Rayford³

et al. 1976

Gut

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SUMMARY We have used a sensitive and specific radioimmunoassay to measure the disappearance half-times of exogenous porcine secretin and endogenous canine secretin in the dog and found them to be 2-45 and 2-85 minutes, respectively.Since the discovery of secretin in 1902 by Bayliss and Starling, quantitative estimations of secretin activity have been based on the ability of the hormone to stimulate flow of bicarbonate-rich pancreatic juice. Since about the time of the initial isolation of the hormone from hog intestine by Jorpes and Mutt (1959), there have been refinements in bioassay technique (Ivy and Janecek, 1959;Mutt and Soderberg, 1959;Heatley, 1968) which have produced considerable standardisation of results. Unfortunately, these techniques lacked specificity and precision, and were incapable of measuring basal levels of secretin in the circulating plasma of animals and man.Calculations of the disappearance half-time (TI) of secretin were, however, made in laboratory animals using pancreatic secretion as an index of secretin activity (Clark et al., 1967;Lehnert et al., 1969;Hubel, 1972).We have recently validated a radioimmunoassay which is both sensitive and specific and can accurately measure concentrations of secretin of less than 20 pg/mi in plasma (Rayford et al., 1976).Using this assay technique, we have measured plasma levels of secretin in dogs after an infusion of pure natural porcine hormone and have calculated its disappearance half-time. We have also measured basal and stimulated levels of endogenous secretin in dogs and have calculated its disappearance halftime. proximately 20 kg were placed in Pavlov stands and an intravenous catheter placed in a foreleg and a hind leg of each dog. After collecting two 5 ml basal blood samples, 10 minutes apart, each dog received an infusion of pure natural secretin (Professor V.Mutt, Gastrointestinal Hormone Laboratory [GIH], Karolinska Institute, Stockholm), 1.5 unit/kg body weight, dissolved in 50 ml 0-9 % NaCI. This secretin preparation contains 3500 clinical units/mg. The infusion was delivered over 30 minutes into a foreleg vein using a Harvard syringe pump. Blood samples were collected from the hind leg catheter at five-minute intervals during the infusion. The infusion was then terminated and samples collected at one-minute intervals for 10 minutes, then at two-minute intervals for 10 minutes. DISAPPEARANCE HALF-TIME OF ENDOGENOUS SECRETINA further six fasting, adult, mongrel dogs were anaesthetized with intravenous sodium pentobarbital ,(25,mg/kg), and the abdomen opened. A segment of bowel, comprising the whole of the duodenum and the proximal 50 cm of the jejunum, was prepared for stimulation of secretin release by ligation of the pylorus, ligation of the superior pancreaticoduodenal vein at its entry into the portal vein, and division of the jejunum and its mesentery 50 cm distal to the ligament of Treitz. A cannula was introduced into the proximal duodenum for infusion of acid, and the distal end of the segment of bowel was left open to allow f...

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Rate and pattern of disappearance of exogenous gastrin in dogs

Cited by 26 publications

References 0 publications

Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

Studies on the Elimination of Secretin and Cholecystokinin with Regard to the Kinetics of Exocrine Pancreatic Secretion

Disappearance half-time of endogenous and exogenous secretin in dogs.

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