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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 1 251-258
Copyright © 2001 by The Endocrine Society

Original Studies

The Predominant Cholecystokinin in Human Plasma and Intestine Is Cholecystokinin-331

J. F. Rehfeld, G. Sun, T. Christensen and J. G. Hillingsø

Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Dr. J. F. Rehfeld, Department Clinical Biochemistry (KB 3011), Rigshospitalet, DK-2100 Copenhagen, Denmark. E-mail: rehfeld{at}rh.dk

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 (~51%) and postprandially (~57%), whereas CCK-22 is the second most abundant (~34% and 30%, respectively). In contrast, CCK-58 is less abundant in human intestines (~18%) and plasma (~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.




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