Cholecystokinin Metabolism in Man and Dogs

Abstract

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.

Variabilities of gallbladder contraction indices and a simple regression model for gallbladder and gastric emptying ratio

“…The serum CCK then promptly returns to baseline due to its rapid metabolism (2.5 minutes serum halftime) [19]. The occurrence of a maximum gallbladder contraction difference of 21% (GBCI10 -GBCI 5) and a decline afterwards is in one accord with this reported 2.5 minute serum half-life of serum CCK.…”

Lack of effect of the specific cholecystokinin receptor antagonist loxiglumide on cholecystokinin clearance from plasma in man.

“…The results suggest that increased plasma CCK concentrations observed after meal stimulation and during bombesin infusion are not the result of impaired metabolism of CCK by loxiglumide. It has previously been shown that circulating peptides like CCK are rapidly metabolised in capillaries throughout the body (Strunz et al, 1978), especially in the kidney (Thompson et al, 1975). However, small molecular forms of CCK are also extracted effectively by the liver (Sakamoto et al, 1985).…”

Cholecystokinin-induced satiety, a key gut servomechanism that is affected by the membrane microenvironment of this receptor

“…This hormone has a very short half-life in the circulation, measured in minutes. 30 This is also the ideal time to stimulate a satiety response when it would be able to limit the size of the meal ingested. Because of the short duration of action of CCK when the physiological hormone needs to be active, accentuation of that response might increase appetite suppression, while not being overly stimulatory and certainly not acting over a longer duration of time that might be associated with trophic effects.…”