Cholecystokinin cleavage to cholecystokinin-octapeptide in vivo and in vitro: accelerated cleavage in acute pancreatitis.

We have examined the possibility that the 33- and 39-amino acid forms of cholecystokinin (CCK) are cleaved to produce CCK-octapeptide (CCK-8) during circulation in humans. When a mixture of the 33- and 39-amino acid forms of porcine CCK was infused at 0.1-2.5 pmol/kg.min into normal subjects, material indistinguishable from CCK-8 by gel filtration and in region-specific radioimmunoassays appeared in plasma, together with an intermediate form that eluted between the 33- and 8-amino acid peptides. During infusions, plasma concentrations of CCK-33/39, CCK-8, and the intermediate CCK rose to 63 +/- 26 (mean +/- SE), 57 +/- 12, and 18 +/- 10 pmol/L, respectively. Cholecystokinin-octapeptide appeared rapidly and constituted approximately 40% of total CCK-like immunoreactivity after 5 min of infusion. Octapeptide-like material also appeared, but at a slower rate, when CCK-33 was incubated at 37 degrees C with human plasma. Thus after 5 min, and throughout the incubation, CCK-8 comprised approximately 20% and CCK-33 approximately 75% of total immunoreactivity. Cholecystokinin-33 disappeared more rapidly and small forms appeared in higher concentrations in plasma from patients with acute pancreatitis. Thus, after incubation for 120 min, CCK-33 and CCK-8 comprised 45% +/- 7% and 13% +/- 3% of initial immunoreactivity in normal plasma, but 18% +/- 6% and 33% +/- 9%, respectively, in plasma from patients with pancreatitis. Ethylenediaminetetraacetic acid, but not aprotinin, inhibited the cleavage of CCK-33 to produce CCK-8, and the degradation of CCK-8 in normal plasma in vitro.