Large and small forms of cholecystokinin in human plasma: measurement using high pressure liquid chromatography and radioimmunoassay.

Defining the role of cholecystokinin (CCK) in gut physiology and disease has proved difficult because of problems with development of radioimmunoassays and because CCK exists in several different molecular forms which have different biological actions. In order to measure small (8 amino acid residues, CCK 8) and large (33 and 39 residues) forms of CCK in plasma we have developed high pressure liquid chromatographic (HPLC) fractionation of plasma prior to radioimmunoassay. Fasting plasma CCK 8 and CCK 33/39 levels were usually undetectable (less than 3 and less than 6 pmol/1, respectively). After a liquid fat meal both CCK 8 and CCK 33/39 levels were significantly elevated at 5 min (11.3 +/- 3.3 and 11.6 +/- 2.6 pmol/1, respectively). Peak CCK 8 levels occurred at 30 min (15.0 +/- 4.4 pmol/1) while peak CCK 33/39 levels occurred at 120 min (16.7 +/- 4.9 pmol/1). Total CCK levels showed a biphasic response to the meal. These CCK 8 and CCK 33/39 responses to oral fat are consistent with a role for these hormones in the regulation of gallbladder emptying and pancreatic secretion.