Large molecular forms of cholecystokinin circulating in humans

Molecular heterogeneity between cholecystokinin (CCK) present in humans and that present in the pig has been proposed. We recently demonstrated that CCK-8 exists in humans in form identical to the porcine peptide. The aims of this work were to evaluate the presence in human plasma of CCK forms larger than CCK-8 and to compare them with the well-characterized porcine forms. Antiserum (no. 4899) was raised in a New Zealand white rabbit immunized with porcine CCK-33 that had specificity for the 7 to 21 region of that peptide and that recognized molecules present in human plasma. To characterize these, postprandial human plasma was applied to an immunoaffinity column generated with this antiserum. Adsorbed peptides were eluted, concentrated on an octadecylsilane cartridge, separated by reversed-phase HPLC and gel filtration chromatography, and screened by cross-reacting and specific CCK and gastrin radioimmunoassays and CCK bioassay by quantification of amylase release by rat pancreatic acini. Two peptides were consistently identified that possessed CCK-like but not gastrin-specific immunoreactivity and CCK-like biological activity. These appeared to be similar in size to CCK-33 and intermediate in size between CCK-33 and CCK-8. Though analogous to porcine CCK based on antibody cross-reactivity and biological activity, the human peptides were heterogeneous from the porcine peptides based on differing chromatographic behavior.