The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33

Cholecystokinin (CCK) occurs in multiple molecular forms; the major ones are CCK-58, -33, -22, and -8. Their relative abundance in human plasma and intestine, however, is debated. To settle the issue, extracts of intestinal biopsies and plasma from 10 human subjects have been examined by chromatography, enzyme cleavages, and measurements using a library of sequence-specific RIAs. Plasma samples were drawn in the fasting state and at intervals after a meal. The abundance of the larger forms varied with the 8 C-terminal assays in the library, as 2 assays overestimated and 3 underestimated the amounts present. One assay, however, measured carboxyamidated and O-sulfated CCKs with equimolar potency before and after tryptic cleavage. This assay showed that the predominant plasma form is CCK-33, both in the fasting state (similar to 51%) and postprandially (similar to 57%), whereas CCK-22 is the second most abundant (similar to 34% and 30%, respectively). In contrast, CCK-58 is less abundant in human intestines (similar to 18%) and plasma (similar to 11%). Its predominance in feline intestines, however, was confirmed. Hence, the results show a significant species variation and emphasize the necessity of highly specific and well characterized assays in molecular studies of CCK.