Hormonal Content and Effect on Gallbladder of Commercial Preparations of Cholecystokinin-Pancreozymin

Summary

The gastrointestinal hormone cholecystokinin-pancreozymin (CCK-PZ) is standardized in biological terms either for its gallbladder-contracting potency (Ivy dog units) - the method usedfor assaying the Karolinska Institute preparation of cholecystokinin, marketed by Kabi Diagnostica, Nykoping, Sweden, or else for its ability to stimulate pancreatic enzyme secretion (Crick Harper Raper units) - the method employed for standardising the Boots pancreozymin preparation (Boots Company Ltd., Nottingham, U.K.). One Ivy dog unit of cholecystokinin has been generally believed to be equivalent to four Crick Harper Raper units of pancreozymin. However, using an in-vitro bioassay technique, we found that one Crick Harper Raper unit of Boots Pancreozymin was about 1.2 times as potent in its effect on the gallbladder as one Ivy dog unit of Cholecystokinin from the Karolinska Institute, instead of having about a quarter of the potency, as expected. Furthermore, the molecular species of cholecystokininin these two preparations are quite different, as shown by gel chromatography and subsequent radioimmunoassay. Boots Pancreozymin containing mainly smaller molecular forms and Karolinska Institute cholecystokinin mainly larger forms of the hormone.

Using the bioassay, qualitative as well as quantitative differences in the gallbladder response to different molecular forms of cholecystokinin were seen, CCK octapeptide (CCK-8) producing faster contraction and faster relaxation after removal of the stimulus than was seen after cholecystokinin (CCK-33). The Boots preparation behaved like CCK-8 and the Karolinska Institute cholecystokinin like CCK-33 in these studies, confirming the gel-chromatography and radioimmunoassay findings.

We conclude that great care must be taken when either of these CCK-PZ preparations is used in clinical or physiological studies, for the results obtained may differ markedly, depending on the preparation used. The belief that one Ivy dog unit of cholecystokinin is equivalent to four Crick Harper Raper units of pancreozymin is probably incorrect.

Key-Words:

Bioassay - Cholecystokinin - Gallbladder - Gastrin - Pancreas - Pancreozymin - Radioimmunoassay - Secretin