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

Cholecystokinin (CCK) occurs in multiple molecular forms; the major ones ar e CCK-58, -33, -22, and -8. Their relative abundance in human plasma and in testine, however, is debated. To settle the issue, extracts of intestinal b iopsies and plasma from 10 human subjects have been examined by chromatogra phy, enzyme cleavages, and measurements using a library of sequence-specifi c RIAs. Plasma samples were drawn in the fasting state and at intervals aft er a meal. The abundance of the larger forms varied with the 8 C-terminal a ssays in the library, as 2 assays overestimated and 3 underestimated the am ounts present. One assay, however, measured carboxyamidated and O-sulfated CCKs with equimolar potency before and after tryptic cleavage. This assay s howed 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 th e second most abundant (similar to 34% and 30%, respectively). In contrast, CCK-58 is less abundant in human intestines (similar to 18%) and plasma (s imilar to 11%). Its predominance in feline intestines, however, was confirm ed. Hence, the results show a significant species variation and emphasize t he necessity of highly specific and well characterized assays in molecular studies of CCK.