We have developed a sensitive, specific and reproducible radioimmunoassay for cholecystokinin (CCK) with which basal levels of CCK of between 400-800 pg/ml have been measured in normal man, in patients with diabetes and with duodenal ulcer disease, and in normal dogs. After a meal, circulating levels of CCK rose to 1000-1200 pg/ml in human subjects. Release of CCK was more rapid in diabetic and duodenal ulcer patients than in normal subjects, but elevated postprandial levels persisted much longer in normal subjects. Patients with the Zollinger-Ellison syndrome had elevated values of cholecystokinin which rose after a meal. Lack of correlation between elevated basal levels of gastrin and CCK in patients with the Zollinger-Ellison syndrome suggest that the hypercholecystokininemia may be absolute. The disappearance half-time of exogenous CCK was about 21/2 minutes in normal subjects as well as in diabetic and duodenal ulcer patients. Studies in dogs demonstrated no uptake of basal levels of cholecystokinin by the kidney; on infusion of exogenous CCK-33, the kidney extracted 43% of the total CCK presented and 56% of the integrated CCK. We conclude that: 1) circulating basal and postprandial levels of CCK may be measured in a reproducible fashion; 2) postprandial release of CCK is more rapid in diabetic and duodenal ulcer patients than in normal man; 3) the disappearance half-time of exogenous CCK in man and dogs is about 21/2 minutes; 4) the kidney is a major site for uptake of CCK.

Five dogs prepared with Heidenhain pouches received infusions of saline, GIP and VIP before and after a standard meat meal. Blood samples were obtained under basal conditions and at subsequent intervals for measurement of gastrin, insulin, GIP and VIP by radioimmunoassay. GIP and VIP infusions had no effect on basal levels of gastrin. GIP and VIP (in common with secretin and glucagon) were found to suppress food-stimulated release of gastrin and gastrin-stimulated acid secretion from the Heidenhain pouch. Insulin levels were significantly elevated during GIP and VIP infusions. Food released GIP (and perhaps VIP.

We have measured serum gastrin and gastric acid secretion in 66 duodenal ulcer patients before and after vagotomy and pyloroplasty (V + P--15 patients), selective proximal vagotomy without drainage (SPV - D--11 patients), and with drainage (SPV + D--19 patients), and vagotomy, antrectomy, and either gastroduodenostomy (V + BI--15 patients) or gastrojejunostomy (V + BII--6 patients). Basal and peak postprandial gastrin levels were increased in postoperative V + P, SPV - D, and SPV + D patients. Basal and peak postprandial levels of gastrin were unchanged after V + BII, indicative of duodenal release of gastrin. Gastrin response to food was abolished in V + BII patients. Acid output was reliably reduced after all five operations; reduction was greatest in patients after antrectomy and least in patients after SPV. No beneficial results were found with drainage in SPV patients. Acid secretion increased with time in SPV patients, especially those with drainage.

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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...