A Decade of Experiences with Radioimmunoassays for Cholecystokinin in the Netherlands

Abstract

The radioimmunologic determination of cholecystokinin (CCK) has proved to be notoriously difficult. This is due to the specificity of antibodies, preparation of radiolabeled CCK and low CCK concentrations in human plasma. About 10 years ago we succeeded in developing two highly sensitive region-specific radioimmunoassays for CCK. Antibody T_2M binds to the sulfated tyrosine region of CCK, while antibody 1703 reacts with biologically active molecular forms of CCK containing at least 14 amino acid residues. Both antibodies are devoid of significant cross-reaction with gastrin. By means of these two radioimmunoassays CCK concentrations were measured in both tissue and plasma of various species, including man. In addition, the molecular forms of CCK in tissue and plasma were characterized. These CCK assays were used to study the mechanism of CCK secretion. It appeared that digested rather than intact protein and fat stimulated CCK release from the small intestine. The physiologic and pathophysiologic role of CCK in humans was studied using CCK radioimmunoassays and specific CCK-receptor antagonists. CCK was found to play an important role in pancreatic enzyme secretion, gallbladder contraction, and gastrointestinal motility but possibly also in pancreatic carcinogenesis and regulation of satiety and satiation.

Key Words:

• Cholecystokinin
• cholecystokinin receptor antagonists
• gallbladder
• gastrointestinal motility
• pancreas
• radioimmunoassay